CARDIOVASCULAR THERAPEUTICS

Compounds and compositions comprising a B-type natriuretic signal peptide fragment agent, and methods of use thereof, are provided for the treatment or prevention of cardiovascular diseases, disorders, and conditions. 1. A pharmaceutical composition for use in preventing and/or treating a cardiovascular disorder , comprising a therapeutically effective amount of a Type-B natriuretic signal peptide fragment agent and a pharmaceutically acceptable carrier.2. A pharmaceutical composition according to claim 1 , wherein said Type-B natriuretic signal peptide fragment agent is BNPsp(17-26) (SEQ ID NO:1).3. A pharmaceutical composition according to claim 1 , wherein said Type-B natriuretic signal peptide fragment agent comprises a sequence selected from SEQ.ID.NOS:2 to 9.4. A pharmaceutical composition according to claim 1 , wherein said composition is suitable for parenteral administration.5. A pharmaceutical composition according to claim 1 , wherein said parenteral administration is infusion.6. A pharmaceutical composition according to claim 1 , wherein said composition is suitable for slow claim 1 , delayed or controlled release administration.7. A pharmaceutical composition according to wherein said cardiovascular disorder is an acute coronary syndrome.8. A pharmaceutical composition according to wherein said cardiovascular disorder is a heart failure or an ischemic heart disease.9. A pharmaceutical composition according to claim 1 , wherein said Type-B natriuretic signal peptide fragment agent comprises a Type-B natriuretic signal peptide fragment analog.10. A pharmaceutical composition according to claim 1 , wherein said Type-B natriuretic signal peptide fragment agent comprises a peptide selected from the group consisting of a peptide according to any one of Formulae I-VIII.11. A substantially pure peptide having the amino acid sequence selected from the group consisting of:{'sub': 1', '2', '3', '4', '5', '6', '7', '8, 'a. L H XXXXXXXX(SEQ ID NO: 19)'}{'sub': 1', ' ...

Tripeptides Incorporating Deuterium as Inhibitors of Hepatitis C Virus

Hepatitis C virus inhibitors having the general formula (I) 2. A compound of wherein each Ris deuterium.3. A compound of wherein each Ris deuterium.4. A compound of wherein each Ris deuterium.5. A compound of wherein each Ris deuterium.6. A compound of wherein Ris deuterium.7. A compound of wherein each Ris deuterium.8. A compound of wherein each Ris deuterium.9. A compound of wherein each Ris deuterium.10. A compound of wherein each Ris deuterium.11. A compound of wherein each Ris deuterium.14. A composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.15. The composition of further comprising at least one additional compound having anti-HCV activity.16. The composition of wherein at least one of the additional compounds is an interferon or a ribavirin.17. The composition of wherein the interferon is selected from interferon alpha 2B claim 16 , pegylated interferon alpha claim 16 , consensus interferon claim 16 , interferon alpha 2A claim 16 , and lymphoblastiod interferon tau.18. The composition of wherein at least one of the additional compounds is selected from interleukin 2 claim 15 , interleukin 6 claim 15 , interleukin 12 claim 15 , a compound that enhances the development of a type 1 helper T cell response claim 15 , interfering RNA claim 15 , anti-sense RNA claim 15 , Imiqimod claim 15 , ribavirin claim 15 , an inosine 5′-monophospate dehydrogenase inhibitor claim 15 , amantadine claim 15 , and rimantadine.19. The composition of wherein at least one of the additional compounds is effective to inhibit the function of a target selected from HCV metalloprotease claim 15 , HCV serine protease claim 15 , HCV polymerase claim 15 , HCV helicase claim 15 , HCV NS4B protein claim 15 , HCV entry claim 15 , HCV assembly claim 15 , HCV egress claim 15 , HCV NS5A protein claim 15 , and IMPDH for the treatment of an HCV infection.20. A method of treating an HCV infection in a ...

COMPOUNDS FOR ENZYME INHIBITION

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles. 2. The method of claim 1 , wherein Z is absent.3. The method of claim 1 , wherein R claim 1 , R claim 1 , and Rare independently selected from hydrogen and methyl.4. The method of claim 1 , wherein L is C═O.5. The method of claim 1 , wherein R claim 1 , R claim 1 , and Rare independently selected from hydrogen claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Chydroxyalkyl claim 1 , Calkoxyalkyl claim 1 , Caralkyl claim 1 , Cheterocycloalkyl claim 1 , Cheteroaralkyl claim 1 , and Ccarbocyclolalkyl.6. The method of claim 5 , wherein any of R claim 5 , R claim 5 , and Rare independently Calkyl.7. The method of claim 6 , wherein any of R claim 6 , R claim 6 , and Rare independently selected from methyl claim 6 , ethyl claim 6 , propyl claim 6 , isopropyl claim 6 , butyl claim 6 , sec-butyl claim 6 , and isobutyl.8. The method of claim 7 , wherein any of R claim 7 , R claim 7 , and Rare independently propargyl.9. The method of claim 5 , wherein any of R claim 5 , R claim 5 , and Rare independently Chydroxyalkyl.10. The method of claim 9 , wherein any of R claim 9 , R claim 9 , and Rare independently selected from hydroxymethyl and hydroxyethyl.11. The method of claim 5 , wherein any of R claim 5 , R claim 5 , and Rare independently Calkoxyalkyl.12. The method of claim 11 , wherein any of R claim 11 , R claim 11 , and Rare independently selected from methoxymethyl and methoxyethyl.13. ...

BIOACTIVE PEPTIDE

The present invention provides a pharmaceutical or a food that comprises, as an active ingredient, at least one peptide selected from the group consisting of Val-Tyr-Leu-Pro-Arg, Tyr-Leu-Pro-Arg, and Leu-Pro-Arg, or an analog thereof. 1. At least one peptide selected from the group consisting of Tyr-Leu-Pro-Arg and Leu-Pro-Arg , or an analog thereof.2. A pharmaceutical or a pharmaceutical composition comprising at least one peptide selected from the group consisting of Val-Tyr-Leu-Pro-Arg , Tyr-Leu-Pro-Arg , and Leu-Pro-Arg , or an analog thereof.3. The pharmaceutical or the pharmaceutical composition according to claim 2 , which is an anxiolytic drug claim 2 , a sleep-inducing drug claim 2 , a sleep-enhancing drug claim 2 , a drug for treating schizophrenia claim 2 , or an antidepressant drug.4. An anxiolytic or sleep-enhancing food comprising at least one peptide selected from the group consisting of Val-Tyr-Leu-Pro-Arg claim 2 , Tyr-Leu-Pro-Arg claim 2 , and Leu-Pro-Arg claim 2 , or at least one analog thereof.5. A method for relieving anxiety or enhancing sleep claim 2 , comprising administering an effective amount of at least one peptide selected from the group consisting of Val-Tyr-Leu-Pro-Arg claim 2 , Tyr-Leu-Pro-Arg claim 2 , and Leu-Pro-Arg claim 2 , or at least one analog thereof to a subject in need thereof. The present invention provides a peptide having a neuromodulatory effect, and a pharmaceutical or a food comprising the peptide.Reflecting today's stressful society, an increasing number of individuals with psychiatric disorders such as anxiety disorders, schizophrenia, and depression has been a problem. Anxiety is inherently necessary as a warning to help living organisms avoid danger. However, it is known that excessive anxiety involves the onset or the progression of symptoms of psychiatric disorders as mentioned above, and also increases the risk of the onset of lifestyle-related diseases. Therefore, the development of foods and pharmaceuticals ...

CHEMICAL LIGATION BY RING OPENING OF OXO-THIOMORPHOLINES

The invention discloses processes for preparing compounds comprising an α-amino acid motif. The compounds are useful in e.g. the chemical ligation of peptides. 2. A process according to wherein compound (IX) is a thioester.4. A process according to wherein Ris an optionally protected peptide.5. A process according to wherein Rcomprises at least a 9H-fluoren-9-ylmethoxycarbonyl (FMOC) protecting group.6. A process according to wherein X is NH.7. A process according to wherein Ris H.8. A process according to wherein Ris H.9. A process according to wherein A is CH.10. A process according to wherein Ris aryl claim 1 , optionally attached to a solid support claim 1 , optionally via a linker.11. A process according to wherein Ris an optionally protected peptide optionally attached to a solid support claim 1 , optionally via a linker.12. A process according to wherein Ris an optionally protected peptide optionally attached to a solid support claim 1 , optionally via a linker.14. A process according to comprising a further deprotection step or steps to give a free peptide.17. (canceled)19. A compound of formula (VI) according to wherein Z is t-butyloxycarbonyl (BOC). The invention relates to processes for the synthesis of molecules comprising an α-amino acid unit, in particular peptides, and to intermediates useful in the synthesis of such compounds.Peptides are of central importance in biological systems. In addition, peptides find use in pharmaceutical, agrochemical and other commercial applications.Chemical synthesis of peptides is a large field of academic endeavour, and many successful approaches to the synthesis of peptides have been developed over the years. The chemical synthesis of peptides allows for the production of the substances on a scale not possible by extraction and purification from natural sources; furthermore, it allows for the incorporation of non-natural amino acids into the peptide structure.Many chemical syntheses of peptides are linear in approach, ...

COMPOUNDS FOR ENZYME INHIBITION

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention. 1. (canceled)3. The method of claim 2 , wherein Rand Rare independently selected from hydrogen and Calkyl.4. The method of claim 3 , wherein Rand Rare both hydrogen.5. The method of claim 4 , wherein Ris selected from methyl claim 4 , ethyl claim 4 , hydroxymethyl claim 4 , and 2-hydroxyethyl.6. The method of claim 5 , wherein Ris methyl.7. The method of claim 2 , wherein Ris hydrogen.8. The method of claim 2 , wherein L and Q are absent.9. The method of claim 2 , wherein Ris selected from —Calkyl-B and Caralkyl.10. The method of claim 9 , wherein Ris selected from methyl claim 9 , ethyl claim 9 , isopropyl claim 9 , carboxymethyl claim 9 , and benzyl.11. The method of claim 2 , wherein Ris selected from Calkyl-phenyl claim 2 , Calkyl-indolyl claim 2 , Calkyl-thienyl claim 2 , Calkyl-thiazolyl claim 2 , and Calkyl-isothiazolyl.13. The method of claim 2 , wherein Ris selected from Calkyl-phenyl and Calkyl-indolyl.15. The method of claim 2 , wherein Ris selected from heterocyclylMZAZ—Calkyl- claim 2 , heterocyclylM- claim 2 , and carbocyclylM-.16. The method of claim 15 , wherein Ris heterocyclylMZAZ—Calkyl- claim 15 , and heterocyclylM-.17. The method of claim 2 , wherein L is C═O claim 2 , Q is absent claim 2 , M is Calkyl and Ris heterocyclylM- and the heterocyclyl moiety is selected from morpholino claim 2 , piperidino claim 2 , piperazino claim 2 , and pyrrolidino.18. The method of claim 17 , wherein L is C═O claim 17 , Q is absent claim 17 , M is Calkyl and Ris heterocyclylM- and the heterocyclyl moiety is morpholino.19. The method of claim 18 , wherein ...

Dimeric Smac Mimetics

The invention provides small molecule mimics of the Smac peptide that are dimers or dimer-like compounds having two binding domains connected by a linker. These compounds are useful to promote apoptosis. The invention includes pharmaceutical compositions comprising such compounds and methods to use them to treat conditions including cancer and autoimmune disorders. 22. A pharmaceutical composition comprising a compound of claim 16 , and at least one pharmaceutically acceptable excipient claim 16 , and further comprising at least one additional therapeutic agent that is TRAIL.23. A method for reducing cell proliferation or inducing cell death claim 16 , comprising contacting a cell with an effective amount of the compound according to claim 16 , thereby reducing cell proliferation or inducing cell death. This application is a continuation of U.S. Ser. No. 12/914,840, filed Oct. 28, 2010, which claims priority to U.S. Ser. No. 61/255,788, filed Oct. 28, 2009 and having the same title and inventors.The present invention relates to dimer and dimer-like small molecule promoters of apoptosis. These compounds mimic the activity of the protein known as Smac, and are thereby able to promote the initiation of apoptosis. The compounds are therefore useful in treating conditions where initiating apoptosis is desirable, such as in pathological cells or tissues. The invention also relates in part to methods for using such compounds, and pharmaceutical compositions containing these compounds.Apoptosis plays a central role in the development and homeostasis of all multi-cellular organisms. Abnormal inhibition of apoptosis is a hallmark of cancer and autoimmune diseases, whereas excessive activation of cell death is implicated in neuro-degenerative disorders such as Alzheimer's disease. Pro-apoptotic chemotherapeutic drugs provide a recent approach to overcoming the clinical problem of drug resistance; see, e.g. Makin et al., . (July 2000) 301(1):143-152 (“Apoptosis and cancer ...

Angiotensin converting enzyme inhibitory peptide

To provide ACE inhibitory peptides which can effectively inhibit ACE by a small amount of ingestion and have no fear of causing side effects and which can be orally ingested easily during daily life by persons having high blood pressure, and compositions comprising the peptides. The peptides represented by the following structural formulae (1) to (9), and salts thereof are provided. (1) Asp-Arg-Pro, (2) Asn-Trp, (3) Val-Gly-Leu, (4) Ile-Gly-Val, (5) Gly-Val-Pro, (6) Ile-Pro-Tyr, (7) pyroGlu-Pro, (8) Tyr-Thr, (9) Pro-Trp

Selective Cysteine Protease Inhibitors and Uses Thereof

The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease). 2. The compound according to claim 1 , in which A is H.3. The compound according to claim 1 , in which A is selected from the group consisting of PhCHOC(O)— claim 1 , Qunoline-C(O)— claim 1 , and (4-amino-3-chlorobenzene)-C(O)—.4. The compound according to claim 1 , in which Z is CORand Ris selected from the group consisting of OH claim 1 , OCH claim 1 , and CHCH5. The compound according to claim 1 , in which Z is CORand Ris OH.6. The compound according to claim 1 , in which a and b are both 0.7. The compound according to claim 1 , in which a is 0 and b is 1.8. (canceled)9. The compound according to claim 1 , in which a is 0 claim 1 , b is 0 and c is 0.10. The compound according to claim 1 , in which a is 0 claim 1 , b is 0 claim 1 , c is 0 and d is 0.11. The compound according to claim 1 , in which Ris in the trans configuration.12. The compound according to claim 1 , wherein Ris{'sub': '2', 'sup': '5', '1) SOR,'}{'sub': '3', 'sup': '5', '2) SOR,'}{'sup': '5', '3) SOR,'}{'sub': '2', 'sup': '5', '4) CORor'}{'sup': '5', '5) COR'}{'sup': '5', 'sub': 1', '6, 'wherein Ris H, C-Calkyl, aryl, or a heterocylyl.'}13. The compound according to claim 1 , in which Ris1) H,2) halogen,3 ...

Method for producing peptide

The present invention provides a production method of peptide, which includes the following step (1). (1) removing N-terminal Fmoc group of N-Fmoc C-protected amino acid or N-Fmoc C-protected peptide wherein a C-terminal carboxy group is protected by an anchor group derived from an anchor soluble in halogenated solvents or ether solvents, insoluble in polar solvents and having a molecular weight of not less than 300, with a non-nucleophilic organic base in a halogenated solvent or ether solvent to give a C-protected amino acid or C-protected peptide, neutralizing with an acid, adding N-Fmoc amino acid or N-Fmoc peptide, a condensing agent and a condensation accelerator to the reaction solution after neutralization, and condensing the N-terminal of the C-protected amino acid or C-protected peptide with N-Fmoc amino acid or N-Fmoc peptide to give an N-Fmoc C-protected peptide.

HEPATOCYTE GROWTH FACTOR (HGF) MIMICS AS THERAPEUTIC AGENTS

Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia, Alzheimer's disease, Parkinson's disease, amyotrphic lateral sclerosis, and other neurodegenerative diseases, spinal cord injury, traumatic brain injury, diabetes and metabolic syndrome, cancer, and defective wound healing. 2. The method of wherein said step of administering is performed multiple times over a period of time.3. The method of further comprising the steps of testing cognition of said subject during said period of time claim 2 , and adjusting an amount of said HGF mimic administered based on test results.4. The method of wherein said HGF mimic is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.5. The method of claim 1 , wherein said subject has Parkinson's disease.7. The method of wherein said HGF mimic is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.8. The method of claim 6 , wherein said subject has Parkinson's disease.10. The method of wherein said HGF mimic is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.11. The method of claim 9 , wherein said subject has Parkinson's disease.13. The method of wherein said HGF mimic is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide. This application claims benefit of U.S. provisional patent applications 61/471,122, filed Apr. 2, 2011; 61/471,124, filed Apr. 2, 2011; and 61/706,567 filed Sep. 27, 2012, the complete contents of each of which are hereby incorporated by reference. The application also claims benefit of and is a continuation-in-part of International patent application PCT/US12/31815 filed Apr. 2, 2012, the complete contents of which is hereby incorporated by reference.This invention was made, in part, with government support under Grant No. MH086032 awarded by National Institues of Health. The United States government has certain ...

Prodrugs of Peptide Epoxy Ketone Protease Inhibitors

This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors. 4. The compound according to claim 1 , wherein M is CH.5. The compound according to claim 1 , wherein said ring nitrogen atom is further substituted with a group R claim 1 , thereby forming a quaternary nitrogen atom and wherein the positive charge associated with the quaternary nitrogen atom is balanced by a pharmaceutically acceptable anion.7. The compound of claim 6 , wherein Ris —CHC(═O)R.8. The compound of claim 7 , wherein Ris Calkyl.9. The compound according to claim 1 , wherein the pharmaceutically acceptable anion is selected from chloride claim 1 , iodide claim 1 , acetate claim 1 , mesylate claim 1 , tosylate claim 1 , and citrate.10. The compound according to claim 2 , wherein Rand Rare each independently Calkyl claim 2 , and Rand Rare each independently Caralkyl.11. The compound according to claim 2 , wherein Rand Rare both isobutyl claim 2 , Ris phenylethyl claim 2 , and Ris phenylmethyl.12. The compound of claim 1 , wherein Ris heteroaryl that includes from 5-6 ring atoms claim 1 , wherein at least one ring atom is a nitrogen atom selected from ═N— and —N(C-Calkyl)- claim 1 , wherein said ring nitrogen atom is further optionally substituted with a group R claim 1 , thereby forming a quaternary nitrogen atom and wherein the positive charge associated with the quaternary nitrogen atom is balanced by a pharmaceutically acceptable anion.14. The compound of claim 12 , wherein Ris:{'sub': '2', 'sup': '15', '(i) —CHC(═O)R;'}{'sub': '2', 'sup': '15', '(ii) —C(═O)OCHC(═O)R;'}{'sup': '15', '(iii) —SR; or'}{'sub': '2', 'sup': '15', '(iv) CHAr—R;'}wherein:{'sub': 6-10', '1-6', '1-6, 'Ar is Caryl, optionally substituted with from 1-3 substituents independently selected from Calkyl, Calkoxy, and halo;'}{'sup': '15', 'sub': 1-6', '1-6', '1-6', '1-6', '6-10', '7-12', '3-7, 'Ris Calkyl, Chaloalkyl, CalkoxyCalkyl, Caryl, Caralkyl, Ccycloalkyl, heteroaryl including from ...

COMPOUNDS FOR ENZYME INHIBITION

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention. 1. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/646,510, filed Oct. 5, 2012, which is a continuation of U.S. patent application Ser. No. 13/328,909, filed Dec. 16, 2011, issued as U.S. Pat. No. 8,357,683 on Jan. 22, 2013, which is a continuation of U.S. patent application Ser. No. 12/708,753, filed Feb. 19, 2010, issued as U.S. Pat. No. 8,080,545 on Dec. 20, 2011, which is a continuation of U.S. patent application Ser. No. 11/820,490, filed Jun. 19, 2007, issued as U.S. Pat. No. 7,691,852 on Apr. 6, 2010, which claims the benefit of U.S. Provisional Application No. 60/815,218, filed Jun. 19, 2006. The contents of these applications are incorporated herein by reference in their entirety.In eukaryotes, protein degradation is predominately mediated through the ubiquitin pathway in which proteins targeted for destruction are ligated to the 76 amino acid polypeptide ubiquitin. Once targeted, ubiquitinated proteins then serve as substrates for the 26S proteasome, a multicatalytic protease, which cleaves proteins into short peptides through the action of its three major proteolytic activities. While having a general function in intracellular protein turnover, proteasome-mediated degradation also plays a key role in many processes such as major histocompatibility complex (MHC) class I presentation, apoptosis and cell viability, antigen processing, NF-κB activation, and transduction of pro-inflammatory signals.The 20S proteasome is a 700 kDa cylindrical-shaped multicatalytic protease complex comprised of 28 subunits, classified ...

Agonists of Neurotrophin Receptors and Their Use as Medicaments

The invention relates to compounds of Formula I: 3. The compound of , wherein Ris fluorophenyl , Ris as defined in , and Ris chosen from propyl , 1-methylethyl , butyl , pentyl , 1-methylbutyl , 2-methylbutyl , hexyl , 4-methylpentyl , 3-methylpentyl , 2-methylpentyl , and 1-methylpentyl.4. The compound of claim 3 , wherein Ris 2-fluorophenyl.5. The compound of claim 1 , wherein Ris pyrrolidin-1-yl.6. The compound of claim 1 , wherein Ris 2-oxo-pyrrolidin-1-ylmethyl.7. The compound of claim 1 , wherein Ris sulfamoylphenyl.825-. (canceled)26. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , and a pharmaceutically acceptable carrier.2739-. (canceled)40. A method of prevention or treatment of nerve cell death or damage; or neuroprotection; or neuroprotection and immunomodulation; or regenerating nerve cells claim 1 , comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.4143-. (canceled)44. A method of prevention or treatment of a disease claim 1 , comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , wherein the disease is selected from: neurological diseases claim 1 , preferentially neurodegenerative disorders claim 1 , such as amyotrophic lateral sclerosis (ALS) claim 1 , Parkinson's disease claim 1 , Alzheimer's disease claim 1 , Friedreich's ataxia claim 1 , Huntington's disease claim 1 , Dementia with Lewy bodies claim 1 , and spinal muscular atrophy; nerve inflammation claim 1 , such as multiple sclerosis or neuromyelitis optica; major depressive disorder; schizophrenia; glaucoma; peripheral neuropathy claim 1 , such as diabetic or AIDS neuropathy; and cancer claim 1 , such as glioblastoma claim 1 , ...

PEPTIDE MOLECULAR MATERIALS

This invention provides a novel peptide molecular material, wherein the molecular structure of the material is a combination of halogen-substituted or unsubstituted aryl and a peptide molecular. This material can self-assemble to form a nanofiber and form a hydrogel. The hydrogel has various properties, including low cytotoxicity, the promotion of cell growth and migration as well as being stable under a physiological condition and a human body temperature. 2. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from a hydrogen atom and C-Caralkyl; x is 1; and y is 1.3. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare independently selected from a hydrogen atom; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl claim 1 , C-Caralkyl and C-Chydroxyaralkyl; x is 1; and y is 2.4. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare independently selected from a hydrogen atom; Rand Rare independently selected from the group consisting of a hydrogen atom and C-Caralkyl; x is 1; and y is 3.5. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl and C-Caminoalkyl; x is 1; and y is 5.6. The peptide molecular material according to claim 1 , wherein A is phenyl; Rand Rare hydrogen atoms; Rand Rare independently selected from a hydrogen atom claim 1 , C-Calkyl and C-Caminoalkyl; x is 0 to 2; and y is 5.7. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl claim 1 , C-Caralkyl and C ...

SITE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses. 295-. (canceled)98. A conjugate of a compound of .99. The conjugate claim 98 , wherein the conjugate protein is CRM.100. The conjugate of claim 98 , wherein the conjugate protein is GBS.101. A vaccine comprising a conjugate of .102. A conjugate of a compound of .103. A vaccine comprising a conjugate of .104. A vaccine comprising a conjugate of .105. A therapeutic protein comprising a compound of .106. A therapeutic protein comprising a compound of .107. An imaging agent comprising a compound of .108. An imaging agent comprising a compound of .109. A labeling tool comprising a compound of .110. A labeling tool comprising a compound of . The present invention relates generally to a novel method of introducing modifying groups to a protein. In particular, the present invention relates to the selective derivation of lysine residues in proteins using a chemoenzymatic microbial transglutaminase-mediated reaction for modifying proteins and methods for their preparation and use.It is well-known that the properties and characteristics of proteins may be modified by conjugating groups to the protein. For example, U.S. Pat. No. 4,179,337 disclosed proteins conjugated to polyethylene or polypropylene glycols. Generally, such conjugation generally requires some functional group in the protein to react with another functional group in a conjugating group. Amino groups, such as the N-terminal amino group or the ε-amino group in lysine residues have been used in combination with suitable acylating reagents for this purpose. It is often desired or necessary to control the conjugation reaction, such as where the conjugating compounds are attached to the protein and to control how many ...

PROLINE COMPOUNDS AS GRANZYME B INHIBITORS

Proline compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided. 6. The compound of claim 5 , or stereoisomer claim 5 , tautomer claim 5 , or pharmaceutically acceptable salt thereof claim 5 , wherein:{'sub': 10', '1', '12, 'R, when defined as C-Calkyl substituted with a carboxylic acid or carboxylate group, is{'sub': 2', 'n', '2, '—(CH)—COH, where n is 2, 3, 4, 5, or 6;'}{'sub': 1', '3', '6', '10, 'optionally wherein one or more single methylene carbons are substituted with a fluoro, hydroxy, amino, C-Calkyl, or C-Caryl group;'}{'sub': 1', '3, 'optionally wherein one or more single methylene carbons are substituted with two fluoro or C-Calkyl groups;'}optionally wherein one or more single methylene carbons are substituted with two alkyl groups that taken together with the carbon to which they are attached form a 3-, 4-, 5-, or 6-membered carbocyclic ring; oroptionally wherein adjacent carbon atoms from an unsaturated carbon-carbon bond or taken together form a benzene ring.8. The compound of claim 5 , or stereoisomer claim 5 , tautomer claim 5 , or pharmaceutically acceptable salt thereof claim 5 , wherein:{'sub': '1', 'Ris tetrazole or triazole;'}{'sub': 2', '2, 'Ra is hydrogen and Rb is selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, hydroxy, C1-C6 alkoxy, aryloxy, aralkoxy, alkylthio, arylthio, arylsulfonyl, and aryl sulfinyl;'}{'sub': 3', '1', '4', '1', '4, 'Ris hydrogen; C-Calkyl optionally substituted with a carboxylic acid, carboxylate, or a carboxylate ester group; or C-Calkyl optionally substituted with an amide, which may be optionally substituted with an alkylheteroaryl group;'}{'sub': 4', '1', '12', '3', '6', '6', '10', '3', '10, 'Ris C-Calkyl, C-Ccycloalkyl, C-Caryl, ...

TRIPEPTIDE EPOXYKETONE COMPOUND CONSTRUCTED BY HETEROCYCLE AND PREPARATION METHOD AND USE THEREOF

Disclosed are a tripeptide epoxyketone compound, a preparation method thereof, and a use thereof in the preparation of anti-tumor drugs. 3. The compound according to claim 2 , characterized in that the compound is:4-(pyrazin-2-yl carbamoyl)piperidin-1-oyl-Phe-Leu-Leu-epoxy ketone;1-(pyrazin-2-oyl)piperidin-4-oyl-Phe-Leu-Leu-epoxy ketone;4-(pyrazin-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;1-(pyrazin-2-oyl)piperidin-4-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyrazin-2-oyl)piperazin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyrazin-2-formamido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-fluorophenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-benzoyl phenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(biphenyl-4-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chlorophenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy phenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(isoxazol-3-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(thiazol-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(1,3,4-thiadizol-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(benzo[d]thiazol-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyridin-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyridin-3-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyridin-4-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyrimidin-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;1-(4-chlorophenyl carbamoyl)piperidin-4-oyl-Leu-Phe-Leu-epoxy ketone;1-(4-methoxy phenyl carbamoyl)piperidin-4-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chlorophenyl carbamoyl)piperazin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy phenyl carbamoyl)piperazin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chloro benzamido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy benzamido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chlorophenyl uramido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy phenyl uramido)piperidin ...

MODULATORS OF PROTEASE ACTIVATED RECEPTORS

The present application provides novel compounds of the Formula (I), pharmaceutical compositions comprising such compounds and methods for using such compounds as tools for biological studies or as agents or drugs for modulating Protease Activated Receptor- (PAR) and for treating a subject at risk of—or susceptible to—a disease or disorder, or having a disease or disorder associated with undesirable PAR activity. 6. The method according to claim 1 , wherein said compound is:5-isoxazoyl-Cha-Ile-aminomethylphenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-methoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3-methoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(4-methoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-methyl)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-ethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-propoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-isopropoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-butoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-isobutoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-chloro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-nitro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-trifluoromethyl)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3-trifluoromethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-trifluoromethyl)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-fluoro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3-fluoro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(4-fluoro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(1,3-dioxalane)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3,4-dichloro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,5-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,3-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,3,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,6-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-methoxy-5-trifluoromethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3,5-bis(trifluoromethyl ...

INDOLINE COMPOUNDS AS GRANZYME B INHIBITORS

Granzyme B inhibitor compounds, compositions that include the compounds, and methods for using the compounds. The compounds of the invention have advantageous water solubility and effectively inhibit Granzyme B. 811-. (canceled)12. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.13. A method for inhibiting Granzyme B in a subject claim 1 , comprising administering an effective amount of a compound of to a subject in need thereof.14. A method for treating a disease claim 1 , disorder claim 1 , or condition treatable by inhibiting Granzyme B claim 1 , comprising administering a therapeutically effective amount of a compound of to a subject in need thereof.15. The method of claim 14 , wherein the disease claim 14 , disorder claim 14 , or condition treatable by inhibiting Granzyme B is selected from treating dissection claim 14 , aneurysm claim 14 , and atherosclerosis.16. The method of claim 14 , wherein the condition treatable by inhibiting Granzyme B is a wound and administering the compound or composition promotes wound healing.17. The method of claim 13 , wherein administering the compound comprises topical administration claim 13 , oral administration claim 13 , and administration by injection. This application is a continuation of U.S. patent application Ser. No. 14/869,750, filed Sep. 29, 2015 (now U.S. Pat. No. 9,605,021), which is a continuation-in-part of International Application No. PCT/CA2014/050317, filed Mar. 28, 2014, which claims the benefit of U.S. Patent Application No. 61/806,767, filed Mar. 29, 2013, and U.S. Patent Application No. 61/941,358, filed Feb. 18, 2014, and is a continuation-in-part of International Application No. PCT/CA2014/050318, filed Mar. 28, 2014, which claims the benefit of U.S. Patent Application No. 61/806,767, filed Mar. 29, 2013, and U.S. Patent Application No. 61/941,358, filed Feb. 18, 2014, each expressly incorporated herein by reference in its entirety.The present ...

PRO-AMB REVERSE TURN RESTRICTED BIOACTIVE PEPTIDE ANALOGUES

The present invention discloses novel peptides acting as angiotensin II analogue for therapeutic applications. Said peptides can be used for treatment of Alzheimer's and other neurological and cognitive disorders. 2. The peptide according to claim 1 , wherein a γ-turn is introduced between 3-amino-2-methoxy benzoic acid (Amb) and Rthrough hydrogen bonding which is stable under aqueous conditions.7. The pharmaceutical composition according to claim 6 , wherein the pharmaceutically acceptable carrier is a physiologically compatible buffer selected from the group consisting of Phosphate buffer saline (PBS) claim 6 , a mixture of saline and glucose and heparinized sodium-citrate-citric acid-dextrose solution.9. The method according to claim 8 , wherein the cognitive disorders is selected from the group consisting of delirium claim 8 , dementia claim 8 , Alzheimer's disease and amnesia and the neurological disorder is dysfunction of the central nervous system and peripheral nervous system. This application claims the benefit of priority of Indian Patent Application No. IN 201611029463, fled Aug. 30, 2016. The contents of which are hereby incorporated herein by reference in their entirety.The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Nov. 22, 2016, is named 1451121_144US2_SL.txt and is 1,367 bytes in size.The present invention relates to a novel peptide analogue for therapeutic applications. More particularly, the present invention relates to an angiotensin II analogue for therapeutic use in treatment of Alzheimer' s and other neurodegenerative diseases.The secondary structure of a protein is characterized by regular elements such as alpha (α) helices, beta (β) sheets and irregular elements such as β bulges, tight turns and random coils. Tight turns are one of the three “classical” secondary structures with approximately one- ...

PSMA-TARGETED NIR DYES AND THEIR USES

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds. 1. A compound having the formula: B—X—Y—Z , whereinB comprises a compound capable of binding to prostate specific membrane antigen (PSMA),X compromises a hydrocarbon chain or hydrocarbon chain with hetero atoms,Y comprises at least one amino acid, or derivative thereof, andZ comprises a near-infra red (NIR) dye.2. The compound of claim 1 , wherein B is selected from the group consisting of a small molecule claim 1 , ligand claim 1 , inhibitor claim 1 , agonist claim 1 , and a derivative thereof.3. The compound of claim 1 , wherein B is 2-[3-(1 claim 1 ,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA) or derivative thereof.4. The compound of claim 1 , wherein X is a hydrophobic spacer.5. The compound of claim 1 , wherein X is a length from 7 atoms to 14 atoms.6. The compound of claim 1 , wherein X is selected from the group consisting of eight aminooctonoic acid (EAOA) claim 1 , polyethylene glycol (PEG) claim 1 , and polyethylene amine (PEA) linker.7. The compound of claim 1 , wherein X is EAOA8. The compound of claim 1 , wherein X is N-amino-dPEG-acid9. The compound of claim 1 , wherein Y comprises negatively charged amino acids.10. The compound of claim 1 , wherein Y comprises positively charged amino acids.11. The compound of claim 1 , wherein Y comprises aromatic amino acids.12. The compound of claim 1 , wherein Z has a positive charge.13. The compound of claim 1 , ...

BORONIC ESTER AND ACID COMPOUNDS, SYNTHESIS AND USES

Disclosed herein is a method for reducing the rate of degradation of proteins in an animal, comprising contacting cells of the animal with certain boronic ester and acid compounds. Also disclosed herein are novel boronic ester and acid compounds, their synthesis and uses. 2. The compound of claim 1 , wherein:A is zero;X is —C(O)—NH—;{'sub': '1-8', 'R is hydrogen or Calkyl; and'}{'sub': 3', '1-6, 'Ris Calkyl.'}3. The compound of claim 2 , wherein Ris Calkyl.4. The compound of claim 1 , wherein:{'sup': 7', '7', '7', '7', '7, 'sub': '2', 'P is R—C(O)— or R—SO—, where Ris one of quinolinyl, quinoxalinyl, pyridyl, pyrazinyl, furanyl or pyrrolyl, or when P is R—C(O)—, Rcan also be N-morpholinyl.'}5. The compound of claim 1 , wherein P is one of quinolinecarbonyl claim 1 , pyridinecarbonyl claim 1 , quinolinesulfonyl claim 1 , quinoxalinecarbonyl claim 1 , quinoxalinesulfonyl claim 1 , pyrazinecarbonyl claim 1 , pyrazinesulfonyl claim 1 , furancarbonyl claim 1 , furansulfonyl or N-morpholinylcarbonyl.6. The compound of claim 5 , wherein P is one of 8-quinolinecarbonyl claim 5 , 8-quinolinesulfonyl claim 5 , 2-quinoxalinecarbonyl claim 5 , 2-quinoxalinesulfonyl claim 5 , 2-pyrazinecarbonyl claim 5 , 2-pyrazinesulfonyl claim 5 , 3-furancarbonyl claim 5 , 3-furansulfonyl or N-morpholinecarbonyl.7. The compound of claim 1 , wherein A is 0.8. The compound of claim 1 , wherein B claim 1 , at each occurrence claim 1 , is CH.9. The compound of claim 8 , wherein X claim 8 , at each occurrence claim 8 , is —C(O)—NH—.10. The compound of claim 9 , wherein Xis —C(O)—NH—.11. The compound of claim 1 , wherein R is hydrogen or Calkyl.12. The compound of claim 1 , wherein:{'sup': 1', '2', '3', '5, 'sub': 1-8', '3-10', '6-10', '2, 'R, at each occurrence, and Rand Rare each independently one of hydrogen, Calkyl, Ccycloalkyl, Caryl, a 5-, 6-, 9- or 10-membered heteroaryl group, or —CH—R;'}{'sup': '5', 'sub': 6-10', '6-10', '1-6', '1-6', '6-10', '3-10', '1-8', '1-8, 'R, in each instance, is ...

PEPTIDE COMPOSITIONS AND METHODS FOR TREATING PATIENTS

The present invention is directed to peptide compositions and methods of using the peptide compositions to treat prediabetes, diabetes, obesity, high blood pressure and metabolic syndrome. 1. A method for treating a condition comprising administering to a patient an effective amount of a composition , wherein the composition comprises:at least one peptide consisting of the amino acid sequence GGL, GLG, LGL, LLG, LGG, GLL, GGdL, GdLG, GdLL, GLdL, GdLdL, dLLG, LdLG, dLdLG, dLGG, dLGL, LGdL, or dLGdL, or a pharmaceutically acceptable salt of the peptide;at least one peptide consisting of the amino acid sequence GGL, GLG, LGL, LLG, LGG, GLL, GGdL, GdLG, GdLL, GLdL, GdLdL, dLLG, LdLG, dLdLG, dLGG, dLGL, LGdL, or dLGdL, or a pharmaceutically acceptable salt of the peptide, wherein the peptide is acetylated at the N-terminus;at least one peptide consisting of the amino acid sequence GGL, GLG, LGL, LLG, LGG, GLL, GGdL, GdLG, GdLL, GLdL, GdLdL, dLLG, LdLG, dLdLG, dLGG, dLGL, LGdL, or dLGdL, or a pharmaceutically acceptable salt of the peptide, wherein the peptide is amidated at the C-terminus; orat least one peptide consisting of the amino acid sequence GGL, GLG, LGL, LLG, LGG, GLL, GGdL, GdLG, GdLL, GLdL, GdLdL, dLLG, LdLG, dLdLG, dLGG, dLGL, LGdL, or dLGdL, or a pharmaceutically acceptable salt of the peptide, wherein the peptide is acetylated at the N-terminus and amidated at the C-terminus; andwherein the condition is prediabetes, diabetes, obesity, high blood pressure, metabolic syndrome, poor glycemic control, or reduced insulin secretion.2. (canceled)3. The method according to claim 1 , wherein the at least one peptide consists of the amino acid sequence GGL claim 1 , GLG claim 1 , LGL claim 1 , LLG claim 1 , LGG claim 1 , GLL claim 1 , or any mixture thereof.4. The method according to claim 1 , wherein the at least one peptide consists of the amino acid sequence GGdL claim 1 , GdLG claim 1 , GdLL claim 1 , GLdL claim 1 , GdLdL claim 1 , dLLG claim 1 , LdLG claim 1 , ...

Inhibitor of Apoptosis Protein (IAP) Antagonists

Provided herein are compounds that modulate the activity of inhibitor of apoptosis proteins (IAPB), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. 3. The compound of any one of - , or pharmaceutically acceptable salt , N-oxide , racemate or stereoisomer thereof , wherein ,—U— is —NHC(═O)—, or —C(═O)NH—;{'sup': '3', 'sub': 1', '3, 'Ris C-Calkyl;'}{'sup': 4', '5', '5', '+', '5, 'sub': 2', '3, 'Ris —NHR, —N(R), or —N(R); and'}{'sup': '5', 'sub': 1', '3', '1', '3', '3', '5, 'each Ris independently selected from H, C-Calkyl, and —C-Calkyl-(C-Ccycloalkyl).'}8. The compound of any one of - , or pharmaceutically acceptable salt , N-oxide , racemate or stereoisomer thereof , wherein Rand Rare independently selected from H and C-Calkyl.10. The compound of any one of - , or pharmaceutically acceptable salt , N-oxide , racemate or stereoisomer thereof , wherein ,{'sup': 2a', '2b', '2c', '2d', 'B, 'sub': 1', '3, 'R, R, R, Rare independently selected from H, C-Calkyl or —C(═O)R; and'}{'sup': B', '3, 'sub': 1', '6', '1', '6', '6', '1', '6', '2', '5', '1', '6', '1', '6, 'Ris substituted or unsubstituted C-Calkyl, —C-Calkyl-(substituted or unsubstituted C-Ccycloalkyl), —C-Calkyl-(substituted or unsubstituted C-Cheterocycloalkyl), —C-Calkyl-(substituted or unsubstituted aryl), or —C-Calkyl-(substituted or unsubstituted heteroaryl).'}11. The compound of any one of - , wherein , R , R , R , Rare independently selected from H , and C-Calkyl.13. The compound of any one of - or - , or pharmaceutically acceptable salt , N-oxide , racemate or stereoisomer thereof , wherein Xis O , S or S(O); and Xis CH.14. The compound of any one of - , or pharmaceutically acceptable salt , N-oxide , racemate or stereoisomer thereof , wherein Ris H or methyl.15. The compound of any one of - , or pharmaceutically acceptable salt , N-oxide , racemate or stereoisomer thereof , wherein Ris H.16. The compound of any one of - , or ...

Biologically active C-terminal arginine-containing peptides

The present invention concerns the separation, identification and characterization of active peptide fragments from peptones. 123-. (canceled)24. A culture medium comprising an isolated C-terminal arginine-containing di- or tri-peptide selected from:a) the tripeptides EVR, DPR, TVR, EIR, ELR, INR, LNR, QVR, AVR, GIR, GLR, IVR, LVR, ITR, LTR, DTR, ESR, GGR, DVR, ILR, LLR, AIR, ALR, ADR, AGR, DQR, ENR, DMR, EMR, GTR, FPR, LMR, IPR, and LPR;b) the tripeptides EVR, VER, LTR, TLR, ITR, TIR, TVR, and VTR; andc) the dipeptides DR, VR, ER, NR, and QR, wherein said peptide exhibits a peptone biological activity.25. The culture medium of claim 24 , wherein said peptide is obtained by fractionation of a peptone or is chemically synthesized.26. The culture medium of wherein said peptide is selected from the peptides EVR claim 24 , DPR claim 24 , TVR claim 24 , EIR claim 24 , ELR claim 24 , INR claim 24 , LNR claim 24 , QVR claim 24 , AVR claim 24 , GIR claim 24 , GLR claim 24 , IVR claim 24 , LVR claim 24 , ITR claim 24 , LTR claim 24 , DTR claim 24 , ESR claim 24 , GGR claim 24 , DVR claim 24 , ILR claim 24 , LLR claim 24 , AIR claim 24 , ALR claim 24 , ADR claim 24 , AGR claim 24 , DQR claim 24 , ENR claim 24 , DMR claim 24 , EMR claim 24 , GTR claim 24 , FPR claim 24 , LMR claim 24 , IPR claim 24 , LPR claim 24 , DR claim 24 , VR claim 24 , ER claim 24 , NR claim 24 , and QR.27. The culture medium of wherein said peptide is a tripeptide.28. The culture medium of wherein said tripeptide is selected from the peptides EVR claim 27 , DPR claim 27 , TVR claim 27 , EIR claim 27 , ELR claim 27 , INR claim 27 , LNR claim 27 , QVR claim 27 , AVR claim 27 , GIR claim 27 , GLR claim 27 , IVR claim 27 , LVR claim 27 , ITR claim 27 , LTR claim 27 , DTR claim 27 , ESR claim 27 , GGR claim 27 , DVR claim 27 , ILR claim 27 , LLR claim 27 , AIR claim 27 , ALR claim 27 , ADR claim 27 , AGR claim 27 , DQR claim 27 , ENR claim 27 , DMR claim 27 , EMR claim 27 , GTR claim 27 , FPR claim 27 , LMR ...

METHODS AND REAGENTS FOR ANALYZING PROTEIN-PROTEIN INTERFACES

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins. 1. A compound comprising:(a) an FKBP binding moiety or cyclophilin binding moiety; and(b) a cross-linking group, wherein the cross-linking group is a sulfhydryl-reactive cross-linking group, an amino-reactive cross-linking group, a carboxyl-reactive cross-linking group, a carbonyl-reactive cross-linking group, or a triazole-forming cross-linking group.2. The compound of claim 1 , wherein the cross-linking moiety is a mixed disulfide claim 1 , a maleimide claim 1 , a vinyl sulfone claim 1 , a vinyl ketone claim 1 , or an alkyl chloride.3. The compound of claim 1 , wherein the interaction between the FKBP binding moiety or cyclophilin binding moiety and FKBP or cyclophilin is non-covalent.4. The compound of claim 1 , wherein the FKBP binding moiety is an FKBP binding moiety capable of binding FKBP12 claim 1 , FKBP12.6 claim 1 , FKBP13 claim 1 , FKBP25 claim 1 , FKBP51 claim 1 , FKBP52 claim 1 , or the cyclophilin binding moiety is a cyclophilin binding moiety capable of binding PP1A claim 1 , CYPB claim 1 , CYPC claim 1 , CYP40 claim 1 , CYPE claim 1 , CYPD claim 1 , NKTR claim 1 , SRCyp claim 1 , CYPH claim 1 , CWC27 claim 1 , CYPL1 claim 1 , CYP60 claim 1 , CYPJ claim 1 , PPIL4 claim 1 , PPIL6 claim 1 , RANBP2 claim 1 , or PPWD1.5. The compound of claim 1 , wherein the FKBP binding moiety or cyclophilin binding moiety is a selective FKBP or cyclophilin binding moiety.6. The compound of claim 1 , wherein the FKBP binding moiety or cyclophilin binding moiety is a non-selective FKBP or cyclophilin binding moiety.9. The compound of claim 1 , wherein the FKBP ...

DMSO-FREE CRYOPRESERVATION SOLUTION AND PREPARATION METHOD AND USE THEREOF

A cryopreservation solution contains 0.01-50.0 g of bionic ice control materials, 5.0-30 mL of polyols, 1-30 g of water-soluble sugar, and 0-30 mL of serum, and a buffer in every 100 mL of the cryopreservation solution. It does not contain DMSO. When being used for the cryopreservation of mouse oocytes and embryos, the solution may achieve the same or an even higher cell and tissue survival rate and functional expression stability as or than a commercial cryopreservation solution (containing 15% DMSO), and has high preservation efficiency. The cryopreservation solution without DMSO or serum reduces parasitic biological contaminants in the commercial cryopreservation solution containing serum currently used in clinical practice. 1. A DMSO-free cryopreservation solution , comprising , per 100 mL , 0.01-50 g of a biomimetic ice growth inhibition material , 5.0-45 mL of a polyalcohol , a water-soluble saccharide at 0.1-1.0 mol L , 0-30 mL of serum and the balance of a buffer , wherein the biomimetic ice growth inhibition material is selected from a PVA and/or an amino acid biomimetic ice growth inhibition material.3. The cryopreservation solution according to claim 1 , wherein the ice growth inhibition material is a PVA claim 1 , and the content of the PVA is 0.1-6.0 g;preferably, the polyalcohol may be C2-5 polyalcohol, such as any one of ethylene glycol, propylene glycol and glycerol;preferably, the water-soluble saccharide may be at least one of a non-reducing disaccharide, a water-soluble polysaccharide and a glycoside, for example, selected from sucrose, water-soluble cellulose (e.g., hydroxypropyl methylcellulose), trehalose and polysucrose;preferably, the buffer may be at least one of DPBS, hepes-buffered HTF buffer and other cell buffers;according to the present invention, the serum can be selected from human serum albumin or a substitute thereof, such as sodium dodecyl sulfate, for a human-derived cryopreservation object, and can be fetal bovine serum or bovine ...

METHOD FOR PREPARING S-Bz-MAG3 AS A PRECURSOR OF CONTRAST MEDIA

The present invention provides a method for preparing S-Bz-MAG3 as a precursor of contrast media. Thioglycolic acid and benzoyl chloride are taken for the thiol protection reaction. Next, N,N′-dicyclohexylcarbodiimide and N-hydroxysuccinimide are converted to corresponding ester compounds. The corresponding ester compounds then react with triglycine by amide bonding reaction. The product of the reaction is recrystallized using acetone, filtered, and finally flushed using flushing agent to give the final product. This is a bifunctional chelator and can be bridged with 99mTc and 186/188Re effectively and applied to nuclear medicine imaging and tumor radiotherapy. By taking advantage of fewer synthesis steps and ease of operations, complicated separation and purification reactions can be reduced and thus achieving highly productivity of S-Bz-MAG3. 1. A method for preparing S-Bz-MAG3 as a precursor of contrast media , comprising steps of:taking thioglycolic acid and benzoyl chloride for performing a thiol protection reaction and producing a first product;taking N,N′-dicyclohexylcarbodiimide and N-hydroxysuccinimide to react with said first product for converting to a second product;taking said second product and triglycine to perform an amide bonding reaction and producing a reaction product;using acetone to recrystallize said reaction product for forming a crystal product;filtering said crystal product; andusing a flushing agent having an alkyl structure to flush the crystal product and producing a final product.2. The method for preparing S-Bz-MAG3 as a precursor of contrast media of claim 1 , and after said step of performing said thiol protection reaction claim 1 , further comprising steps of:filtering said first product and flushing said first product using water; anddrying said first product for increasing the productivity of said first product.3. The method for preparing S-Bz-MAG3 as a precursor of contrast media of claim 1 , wherein said first product is S- ...

SELECTIVE DRUG RELEASE FROM INTERNALIZED CONJUGATES OF BIOLOGICALLY ACTIVE COMPOUNDS

The invention relates to conjugates of biologically active compounds, wherein such a conjugate is comprised of a sequence of amino acids containing a tripeptide that confers selective cleavage by tumor tissue homogenate for release of free drug and/or improves biodistribution into the tumor tissue in comparison to normal tissue homogenate from the same species, wherein the normal tissue is the site of an adverse event associated with administration to a human subject in need thereof of a therapeutically effective amount of a comparator conjugate whose amino acid sequence is a dipeptide known to be selectively cleavable by Cathepsin B. 3. The Ligand Drug Conjugate composition of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein HE is —C(═O)—.6. The Ligand Drug Conjugate composition of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein the secondary amine-containing auristatin compound is monomethylauristatin E (MMAE) or monomethylauristatin F (MMAF).8. The Ligand Drug Conjugate composition of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein the Peptide Cleavable Unit is a tripeptide having the sequence -P3-P2-P1- claim 1 , wherein P1 claim 1 , P2 claim 1 , and P3 are each an amino acid claim 1 , wherein:the P3 amino acid of the tripeptide is in the D-amino acid configuration;one of the P2 and P1 amino acids has an aliphatic side chain with hydrophobicity lower than that of leucine; andthe other of the P2 and P1 amino acids is negatively charged.9. The Ligand Drug Conjugate composition of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein the P3 amino acid is D-Leu or D-Ala.10. The Ligand Drug Conjugate composition of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein one of the P2 or P1 amino acid has an aliphatic side chain with hydrophobicity no greater than that of valine claim 1 , and the other of the P2 or P1 amino acid is negatively charged at ...

AGONISTS OF NEUROTROPHIN RECEPTORS AND THEIR USE AS MEDICAMENTS

The invention relates to compounds of Formula I: 3. The compound of , wherein Ris fluorophenyl , Ris as defined in , and Ris chosen from propyl , 1-methylethyl , butyl , pentyl , 1-methylbutyl , 2-methylbutyl , hexyl , 4-methylpentyl , 3-methylpentyl , 2-methylpentyl , and 1-methylpentyl.4. The compound of claim 3 , wherein Ris 2-fluorophenyl.5. The compound of claim 1 , wherein Ris pyrrolodin-1-yl.6. The compound of claim 1 , wherein Ris 2-oxo-pyrrolidin-1-ylmethyl.7. The compound of claim 1 , wherein Ris sulfamoylphenyl.8. The compound of claim 7 , wherein Ris 4-sulfamoylphenyl.925-. (canceled)26. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of at least one compound of claim 1 , and a pharmaceutically acceptable carrier.2759-. (canceled)60. A method of preparing a pharmaceutical composition claim 1 , comprising admixing an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , with a pharmaceutically acceptable carrier. This application claims the benefit of the earlier filing date of U.S. Provisional Application No. 61/378,823, filed Aug. 31, 2010, the entirety of which is incorporated by reference herein.Field of InventionThis invention applies to the area of therapeutics for neurological, psychiatric disorders, and ageing. In particular, it relates to the neuroprotective effect of small molecule agonists of neurotrophin (Nerve Growth Factor (NGF) or Brain-Derived Neurotrophic Factor (BDNF)) receptors and the use of those agonists as medicaments.Background ArtAgeing, neurological and psychiatric disorders cause death and damage to nerve cells. Frequent and relevant damage to the nervous system can result from neuronal degeneration, ischemia, inflammation, immune responses, trauma, and cancer, among other things. As a consequence of these, nerve cells can die within minutes or hours or survive this initial damage in an impaired state that activates neurodegeneration, ...

PEPTIDE ACETALS FOR STABILISING ENZYMES

The present invention relates to a compound for stabilizing enzymes, the use of said compound for stabilizing an enzyme, a composition comprising said compound, a method of preparing the composition comprising said compound, a detergent composition comprising said compound and a method of preparing said compound. 2. Compound according to claim 1 , wherein Rand Ris a group such that NH—CHR—CO and NH—CHR—CO is an L or D-amino acid residue of Gly claim 1 , Ala claim 1 , Val claim 1 , Leu claim 1 , Ile claim 1 , Met claim 1 , Pro claim 1 , Phe claim 1 , Trp claim 1 , Ser claim 1 , Thr claim 1 , Asp claim 1 , Gln claim 1 , Tyr claim 1 , Cys claim 1 , Lys claim 1 , Arg claim 1 , His claim 1 , Asn claim 1 , Glu claim 1 , m-tyrosine claim 1 , 3 claim 1 ,4-dihydroxyphenylalanine claim 1 , Nva claim 1 , or Nle.3. Compound according to claim 1 , wherein Ris a group such that NH—CHR—CO is an L or D-amino acid residue of Gly claim 1 , Ala claim 1 , Val claim 1 , Leu claim 1 , Ile claim 1 , Met claim 1 , Pro claim 1 , Phe claim 1 , Trp claim 1 , Ser claim 1 , Thr claim 1 , Asp claim 1 , Gln claim 1 , Tyr claim 1 , Cys claim 1 , Lys claim 1 , Arg claim 1 , His claim 1 , Asn claim 1 , Glu claim 1 , m-tyrosine claim 1 , 3 claim 1 ,4-dihydroxyphenylalanine claim 1 , Nva claim 1 , or Nle claim 1 , or wherein Ris (CH)SiCH.4. Compound according to claim 1 , wherein Ris a group such that NH—CHR—CO is an L or D-amino acid residue of Ala claim 1 , Val claim 1 , Gly claim 1 , Arg claim 1 , Leu claim 1 , Phe or Thr.5. Compound according to claim 1 , wherein Ris a group such that NH—CHR—CO is an L or D-amino acid residue of Ala claim 1 , Cys claim 1 , Gly claim 1 , Pro claim 1 , Ser claim 1 , Thr claim 1 , Val claim 1 , Nva or Nle.6. Compound according to claim 1 , wherein Ris a group such that NH—CHR—CO is an L or D-amino acid residue of Tyr claim 1 , m-tyrosine claim 1 , 3 claim 1 ,4-dihydroxyphenylalanine claim 1 , Phe claim 1 , Val claim 1 , Ala claim 1 , Met claim 1 , Nva claim 1 , Leu ...

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed 2. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is C-Calkyl.3. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is methyl or ethyl.4. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein said C-Ccarbocyclene is optionally substituted with C-Calkyl or C-Chaloalkyl.5. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein the C-Ccarbocyclene is optionally substituted with methyl claim 1 , ethyl or trifluoromethyl.6. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is cyclopropylene.7. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Cbridged bicyclic carbocyclylene or C-Cfused bicyclic carbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons.8. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is ...

DISCOVERY OF THE FIRST SELECTIVE C5A2 RECEPTOR (C5L2/C5AR2) LIGANDS

A method of selectively modulating the activity of C5a receptor 2 (C5aR2). The method includes exposing the receptor to a compound that selectively modulates C5aR2 compared to C5a receptor 1 (C5aR1). In some cases, the compound is peptide P32 or P59. Methods of recruiting β-arrestin 2 in a cell, modulating C5a-induced ERK1/2 activation in a macrophage, selectively inhibiting the release of IL-6 from a macrophage, are also provided. 1. A method of selectively modulating the activity of C5a receptor 2 (C5aR2) , comprising exposing the receptor to a C5aR2 ligand that selectively modulates C5aR2 compared to C5a receptor 1 (C5aR1).2. The method of claim 1 , wherein the C5aR2 is on the surface of or inside a cell.3. The method of claim 2 , wherein the cell is in a subject or in culture.4. The method of claim 1 , wherein the ligand acts as a C5aR2 agonist or antagonist.5. The method of claim 1 , wherein the ligand is a polypeptide or peptide comprising SEQ ID NO:1 or SEQ ID NO:2.6. The method of claim 1 , wherein the ligand is a peptide comprising SEQ ID NO:1 or SEQ ID NO:2 claim 1 , or an analog claim 1 , sequence variant claim 1 , peptide surrogate claim 1 , or peptidomimetic of the peptide.7. A method of recruiting β-arrestin 2 in a cell claim 1 , modulating C5a-induced ERK1/2 activation in a macrophage claim 1 , selectively inhibiting release of IL-6 from a macrophage claim 1 , or any combination thereof claim 1 , comprising exposing the cell or macrophage to a C5aR2 ligand that selectively modulates C5aR2 compared to C5aR1.8. The method of claim 7 , wherein the cell or macrophage is in culture or in a subject.9. The method of claim 7 , wherein the ligand is a polypeptide or peptide comprising SEQ ID NO:1 or SEQ ID NO:2.10. The method of claim 7 , wherein the ligand is a peptide comprising SEQ ID NO:1 or SEQ ID NO:2 claim 7 , or an analog claim 7 , sequence variant claim 7 , peptide surrogate claim 7 , or peptidomimetic of the peptide.11. A method of treating a disease ...

Preparation of Technetium-99M Tricarbonyl Labeled Glycine Monomer or Oligomer Containing Probes That Have Biomolecules and Its Application as Imaging Complex-Composition

Disclosed is a technetium-99m-labeled glycine oligomer associated with imaging probes for biomolecules of interest. The glycine oligomer can be readily synthesized in a single process using an automated peptide synthesizer. The technetium-99m tricarbonyl-labeled glycine oligomers can be useful as a radiotracer for gamma or SPECT imaging apparatus. The technetium-99m tricarbonyl-labeled glycine oligomers can be applied to various peptidyl biomolecules such as RGD peptide, somatostatin, neurotensin, etc., and exhibit rapid renal clearance without being excessively retained within the body. 1. A method for preparing a technetium-99m-labeled monomer or oligomer , comprising:a) synthesizing a technetium-99m tricarbonyl precursor; andb) labeling a glycine monomer or oligomer with the technetium-99m tricarbonyl precursor.2. The method of claim 1 , wherein the glycine oligomer is a glycine trimer or a glycine pentamer.3. The method of claim 1 , wherein the glycine monomer or oligomer is further conjugated into a targeted peptide.4. The method of claim 3 , wherein the targeted peptide is selected from the group consisting of an RGD peptide (arginylglycylaspartic acid) claim 3 , neurotensin claim 3 , somatostatin claim 3 , angiotensin claim 3 , luteinizing hormone releasing hormone claim 3 , insulin claim 3 , oxytocin claim 3 , neurokinin-1 claim 3 , vasoactive intestinal peptide claim 3 , substance P claim 3 , neuropeptide Y claim 3 , endothelin A claim 3 , endothelin B claim 3 , bradykinin claim 3 , interleukin-1 claim 3 , epidermal growth factor claim 3 , cholecystokinin claim 3 , galanin claim 3 , melanocyte-stimulating hormones claim 3 , lanreotide claim 3 , octreotide claim 3 , and arginine-vasopressin. The present invention relates to a method for preparing a technetium-99m tricarbonyl-labeled glycine monomer or oligomer in a single process using automated peptide synthesis, and an imaging contrast composition containing the technetium-99m tricarbonyl-labeled glycine ...

Cardiovascular Therapeutics

Compounds and compositions comprising a B-type natriuretic signal peptide fragment agent, and methods of use thereof, are provided for the treatment or prevention of cardiovascular diseases, disorders, and conditions. 1. A pharmaceutical composition for use in preventing and/or treating a cardiovascular disorder , comprising a therapeutically effective amount of a Type-B natriuretic signal peptide fragment agent and a pharmaceutically acceptable carrier.210.-. (canceled)11. A substantially pure peptide having the amino acid sequence selected from the group consisting of{'br': None, 'sub': 1', '2', '3', '4', '5', '6', '7', 'g, 'LH XXXXXXXX\u2003\u2003a.'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8, 'claim-text': {'br': None, 'sub': 1', '2', '3', '4', '5', '6', '7, 'LH XXXXXXX\u2003\u2003b.'}, 'wherein Xis Norleucine, Ile, Val, Met, Ala, Phe or Gly; Xis Val, Leu or Ile or Gly; Xis Leu, Val, Ile, Ala, Tyr or Gly; Xis Norleucine, Ile, Val, Met, Ala, Phe or Gly; Xis Pro, Ala, Arg or Ser; Xis Pro, Ala, Arg or Ser; Xis Gln, Asn or Gly; and Xis Ser, Thr or Gly;'}{'sub': 1', '2', '3', '4', '5', '6', '7, 'wherein Xis Norleucine, Ile, Val, Met, Ala, Phe or Gly; Xis Val, Leu, Ile or Gly; Xis Leu, Val, Ile, Ala, Tyr or Gly; Xis; Norleucine, Ile, Val, Met, Ala, Phe or Gly; Xis Pro, Ala, Arg or Ser; Xis Pro, Ala, Arg or Ser; and Xis Arg, Gln, Asn or Gly; provided that'}{'sub': 1', '2', '3', '4', '5', '6', '7, 'where Xis Norleucine, Ile, Val, Met, Ala, Phe or Gly, Xcan also be Ala, Xcan also be Phe, Xcan also be Leu, Xcan also be Gly, Xcan also be Gly, and Xcan also be Arg;'}{'sub': 2', '1', '3', '4', '5', '6', '7, 'where Xis Val, Leu or Ile or Gly, Xcan also be Leu, Xcan also be Phe, Xcan also be Leu, Xcan also be Gly, Xcan also be Gly, and Xcan also be Arg;'}{'sub': 3', '1', '2', '4', '5', '6', '7, 'where Xis Leu, Val, Ile, Ala, Tyr or Gly, Xcan also be Leu, Xcan also be Ala, Xcan also be Leu, Xcan also be Gly, Xcan also be Gly, and Xcan also be Arg;'}{'sub': 4', '1', '2', '3', ...

CROSS-LINKERS AND THEIR USES

Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same. 126-. (canceled)28. The method of claim 27 , wherein the method is for treating ovarian cancer.29. The method of claim 28 , wherein one of R claim 28 , R claim 28 , R claim 28 , R claim 28 , R claim 28 , and Ris a charged substituent selected from SO claim 28 , X—SO claim 28 , OPO claim 28 , X—OPO claim 28 , NRRRand X—NRRR claim 28 , and the rest are H; l claim 28 , g and m are each 0; and n is 1.30. The method of claim 28 , wherein one of R claim 28 , R claim 28 , R claim 28 , R claim 28 , R claim 28 , and Ris SO or X—SO claim 28 , the rest are H; l claim 28 , g and m are each 0; and n is 1.31. The method of claim 28 , wherein the cell-binding agent is an antibody or an antibody fragment that binds to a target cell.32. The method of claim 31 , wherein the cell-binding agent is a resurfaced antibody claim 31 , a resurfaced single chain antibody claim 31 , or a resurfaced antibody fragment thereof.33. The method of claim 31 , wherein the cell-binding agent is a monoclonal antibody claim 31 , a single chain monoclonal antibody claim 31 , or a monoclonal antibody fragment thereof.34. The method of claim 31 , wherein the cell-binding agent is a human antibody claim 31 , a humanized antibody or a resurfaced antibody claim 31 , a humanized single chain antibody claim 31 , or a humanized antibody fragment thereof.35. The method of claim 31 , wherein the cell-binding agent is a chimeric antibody claim 31 , a chimeric antibody fragment claim 31 , a domain antibody claim 31 , or a domain antibody fragment thereof.37. The method of claim 36 , wherein the cytotoxic agent is a maytansinoid.39. The method of claim 38 , wherein the cell-binding agent is an antibody that binds to a folate receptor.40. The method of claim 39 , wherein the folate receptor is FOLR1 (folate receptor 1). This application ...

HEPATITIS C VIRUS INHIBITORS

The present disclosure relates to methods for making asunaprevir, useful treatment of Hepatitis C virus (HCV) infection, and its intermediates. 2. The process of further comprising treating the reaction mixture of step (a) with water and methyl tert-butyl ether.3. The process of further comprising distilling the isolated organic phase.4. The process of wherein the isolated organic phase is seeded with crystals of the compound of formula (I).65. The process of claim () further comprising quenching step (a) with sodium phosphate monobasic.7. The process of further comprising distilling the isolated organic phase.8. The process of wherein the isolated organic phase is treated with acetic acid and then seeded with crystals of the compound of formula (II). This application claims priority to U.S. Provisional Patent Application Ser. No. 62/016,952, filed Jun. 25, 2014, which is incorporated by reference in its entirety.The present disclosure relates to methods for making asunaprevir, useful in the treatment of Hepatitis C virus (HCV) infection, and its intermediates.Approximately 170 million people worldwide are chronically infected with hepatitis C virus (HCV), including approximately 4 million in the United States. The majority of individuals infected progress to chronic hepatitis, which can lead to cirrhosis, liver failure, and hepatocellular carcinoma (HCC). HCV is the leading indication for liver transplantation in most countries and a major cause of HCC.There are 6 major HCV genotypes with many subtypes based on sequence heterogeneity of the genome. Genotypes (GT) 1-3 have a worldwide distribution (with GT-1 being the major genotype in the United States, Europe, Japan, and South America), GTs-4 and -5 are found principally in Africa, and GT-6 is distributed primarily in Asia. Although genotype does not predict the outcome of infection, different GT are associated with differential responses to treatment, and allow dosage of current interferon (IFN)-based treatment ...

COMBINATION THERAPY FOR TREATING HCV INFECTION IN AN HCV-HIV COINFECTED PATIENT POPULATION

The present invention relates to therapeutic combinations comprising (a) Compound (1), or a pharmaceutically acceptable salt thereof, as herein described, (b) an interferon alfa and (c) ribavirin. Compound (1) is a selective and potent inhibitor of the HCV NS3 serine protease. The present invention also relates to methods of using such therapeutic combinations for treating HCV infection or alleviating one or more symptoms thereof in a patient that is co-infected with HIV. 2. The method according to claim 1 , wherein the patient has HCV subtype 1.3. The method according to claim 1 , wherein the patient has HCV subtype 1a.4. The method according to claim 1 , wherein the patient has an HIV-1 infection.5. The method according to claim 1 , wherein the patient is already on anti-retroviral therapy.6. The method according to claim 1 , wherein said patient is a treatment-naive patient.7. The method according to claim 1 , wherein said patient is a treatment experienced patient.8. The method according to claim 1 , wherein the HCV-RNA levels of said patient are reduced to a less than detectable level as a result of the treatment.9. The method according to claim 1 , wherein said therapeutic combination is administered for at least 4 weeks.10. The method according to claim 1 , wherein said therapeutic combination is administered for at least 12 weeks.11. The method according to claim 1 , wherein said therapeutic combination is administered for at least 24 weeks.12. The method according to claim 1 , wherein compound (1) or a pharmaceutically acceptable salt thereof is administered at a maintenance dosage of at least 40 mg per day.13. The method according to claim 1 , wherein compound (1) or a pharmaceutically acceptable salt thereof is administered at a maintenance dosage between about 40 mg per day and about 480 mg per day.14. The method according to claim 1 , wherein compound (1) or a pharmaceutically acceptable salt thereof is administered at a maintenance dosage between about ...

ANTI-INFLAMMATORY TRIPEPTIDES

The present invention relates to tripeptide compounds according to the general formula (1) and their use as a medicament, in particular as anti-inflammatory agents. 2. The tripeptide compound according to claim 1 , selected from the group consisting of H-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-OH claim 1 , N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-OH claim 1 , N claim 1 ,N-dimethyl-(L)-Lys-(p)-Pro-N-methyl-(L)-Thr-NH claim 1 , and N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Val-OH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.3. The tripeptide compound according to claim 1 , wherein the tripeptide compound is N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-OH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.4. The tripeptide compound according to claim 1 , wherein the tripeptide compound is N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-NH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.5. The tripeptide compound according to claim 1 , wherein the tripeptide compound is N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Val-OH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.6. A method of therapeutic and/or prophylactic treatment of disease claim 1 , comprising: administering the tripeptide compound according to .7. The method of claim 6 , wherein the disease is selected from the group consisting of: an acute inflammatory disease claim 6 , a chronic inflammatory disease claim 6 , acute pain claim 6 , chronic pain claim 6 , pruritus claim 6 , hyponatremia claim 6 , edema claim 6 , ileus claim 6 , tussis claim 6 , and glaucoma.8. The method of claim 7 , wherein the inflammatory disease is selected from the group consisting of: cardiovascular inflammation claim 7 , neurological inflammation claim 7 , skeletal inflammation claim 7 , skin inflammation claim 7 , muscular inflammation ...

COMPOSITIONS AND METHODS FOR INHIBITING PROTEASES

In particular, in alternative embodiments, the invention provides pharmaceutical compounds and formulations comprising a family of epoxyketone compounds, which include racemic mixtures or racemates, isomers, stereoisomers, diastereoisomers, derivatives and analogs, and methods for making and using them. In alternative embodiments, pharmaceutical compositions and formulations of the invention are administered to an individual in need thereof in an amount sufficient to treat, prevent, reverse and/or ameliorate an infection, disease or condition that can be ameliorated, treated, prevented or reversed by partially or completely inhibiting a chymotrypsin-like protease or a proteasome activity, including e.g., a retroviral infection such as human immunodeficiency virus-1 (HIV-1) infection, an immune disorder, a neurodegenerative disease or condition, or a cancer such as a myeloma or multiple myeloma, an adenocarcinoma such as a lung adenocarcinoma, a pancreatic cancer, a B-cell related cancer, and lymphomas such as non-Hodgkin's lymphoma. 2. The compound of claim 1 , formulated as a pharmaceutical composition for enteral or parenteral administration.3. The compound of claim 1 , wherein the compound has four stereocenters.4. A formulation or a pharmaceutical composition comprising a compound or composition of .5. A method for inhibiting a proteasome claim 1 , or a chymotrypsin-like activity of a 20S proteasome claim 1 , comprising administering to a cell or contacting a cell with an effective amount of a compound claim 1 , a composition or a formulation of .6. A method for treating claim 1 , preventing claim 1 , partially reversing or reversing and/or ameliorating a condition claim 1 , disease or infection that can be ameliorated claim 1 , treated claim 1 , prevented or reversed by partially or completely inhibiting a proteasome activity claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) administering a compound, composition or formulation of , in ...

PHARMACEUTICAL COMPOSITION FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE COMPRISING THE PEPTIDE HAVING THE ABILITY TO INHIBIT ANGIOTENSIN-1 CONVERTING ENZYME AS AN ACTIVE INGREDIENT

The present invention relates to a peptide separated from the fraction of oyster enzyme hydrate displaying the ability of suppressing angiotensin converting enzyme (ACE) and a pharmaceutical composition for the prevention and treatment of cardiovascular disease comprising the said peptide as an active ingredient. Particularly, the peptide separated from the fraction of the oyster enzyme hydrate of the present invention significantly inhibits ACE activity, and thus brings blood pressure regulating effect and antihypertensive effect. Therefore, the fraction of the oyster enzyme hydrate of the invention or the peptide separated from the same can be effectively used as an active ingredient of a pharmaceutical composition for the prevention or treatment of cardiovascular disease. 1. A method for treating cardiovascular disease containing the step of administering at least one of the peptides having the amino acid sequences represented by SEQ ID NOs: 1˜12 to a subject having cardiovascular disease.2. The method according to claim 1 , wherein the peptide is separated from the oyster enzyme hydrate.3. The method according to claim 2 , wherein the enzyme is protease.4. The method according to claim 1 , wherein the peptide inhibiting angiotensin converting enzyme (ACE).5. The method according to claim 1 , wherein the cardiovascular disease is one or more diseases selected from the group consisting of hypertension claim 1 , heart disease claim 1 , stroke claim 1 , thrombosis claim 1 , angina pectoris claim 1 , heart failure claim 1 , myocardial infarction claim 1 , atherosclerosis claim 1 , and arteriosclerosis.6. A method for treating cardiovascular disease containing the step of administering a fraction of the oyster enzyme hydrate containing the peptide comprising one of the amino acid sequences represented by SEQ ID NOs: 1˜NO: 12 to a subject having cardiovascular disease.7. The method according to claim 6 , wherein the fraction is up to 10 kD.8. The method according to ...

ACH-0142684 SODIUM SALT POLYMORPH, COMPOSITION INCLUDING THE SAME, AND METHOD OF MANUFACTURE THEREOF

The disclosure provides a crystalline sodium salt of ACH-0142684 comprising a Form A polymorph, a Form B polymorph, a Form C polymorph, a Form D polymorph, a Form E polymorph, a Form F polymorph, a Form G polymorph, a Form H polymorph, a Form I polymorph, or a combination thereof, wherein the Form A, B, C, D, E, F, G, H, and I polymorph exhibits an X-ray powder diffraction pattern having peak locations in accordance with FIGS. , and , respectively. 1. The crystalline form of the sodium salt of ACH-1042684 comprising polymorph A.2. The crystalline form of the sodium salt of ACH-1042684 of wherein{'figref': {'@idref': 'DRAWINGS', 'FIG. 8'}, 'polymorph A exhibits an X-ray powder diffraction pattern having the characteristic 2θ values of .'}3. The crystalline form of the sodium salt of ACH-0142684 of claim 1 , wherein polymorph A is characterized by an X-ray powder diffraction pattern obtained from a Cu Kα source which comprises peaks at 2θ values of 6.4 claim 1 , 16.3 claim 1 , 18.8 claim 1 , 21.8 claim 1 , and 23.7+/−0.2; or 10.1 claim 1 , 17.4 claim 1 , 20.5 claim 1 , 21.6 claim 1 , 23.0 claim 1 , and 24.5+/−0.2; or 11.6 claim 1 , 18.3 claim 1 , 21.6 claim 1 , 23.0 claim 1 , and 25.4+/−0.2.4. The crystalline form of the sodium salt of ACH-0142684 of claim 1 , wherein polymorph A has a primary endotherm at 231.4° C. as determined by DSC.5. The crystalline form of the sodium salt of ACH-0142684 of claim 1 , wherein polymorph A has a Raman spectrum with the characteristic values of .6. The crystalline form of the sodium salt of ACH 1042684 comprising polymorph B.7. The crystalline form of the sodium salt of ACH-0142684 of claim 6 , wherein polymorph B exhibits an X-ray powder diffraction pattern having the characteristic 2θ values of .8. The crystalline form of the sodium salt of ACH-0142684 of claim 6 , wherein polymorph B is characterized by an X-ray powder diffraction pattern obtained from a Cu Kα source which comprises peaks at 2θ values of 5.6 claim 6 , 6.8 claim 6 ...

DIPEPTIDYL PEPTIDASE-IV (DPPIV), INHIBITORY PEPTIDE COMPOUND, COMPOSITION CONTAINING THE SAME, AND PRODUCTION METHOD FOR THE SAME

A peptide compound having a dipeptidyl peptidase-IV (DPPIV) inhibitory activity or a composition containing the peptide compound that can make a contribution to the prevention of the onset of pathology or the progression in diabetes mellitus patients or those at risk of diabetes mellitus can be provided according to the present invention by a simple method using, as a raw material, milt of a fishery product, which has been eaten for ages and has high safety. In the present invention, a peptide compound having a peptidyl peptidase-IV (DPPIV) inhibitory activity obtained in a hydrolysate of a milt protein source obtained from a fishery product is used as an active component of a composition for inhibiting DPPIV. 1. A composition for inhibiting dipeptidyl peptidase-IV (DPPIV) , comprising a peptide compound having a DPPIV inhibitory activity obtained by hydrolysis of a protein source derived from milt of a fishery product.2. The composition according to claim 1 , wherein the fishery product is one or more of salmon claim 1 , pink salmon claim 1 , herring claim 1 , pacific cod claim 1 , skipjack claim 1 , yellowtail (young yellowtail) and squid.3. The composition according to claim 1 , wherein the peptide compound has the effect of inhibiting increase in blood glucose level by the DPPIV inhibitory activity.4. The composition according to claim 1 , wherein the protein source derived from the milt of a fishery product is a protein source comprised in an extraction residue obtained as a by-product in extraction of protamine and/or DNA from milt of a fishery product.5. The composition according to claim 1 , comprising claim 1 , as the peptide compound claim 1 , at least one peptide selected from the group consisting of Phe-Pro-Val-Gly and salts thereof claim 1 , Ile-Pro-Leu and salts thereof claim 1 , Leu-Pro-Val-Leu and salts thereof claim 1 , and Val-Pro-Phe-Pro and salts thereof.6. A composition for inhibiting dipeptidyl peptidase-IV (DPPIV) claim 1 , comprising claim 1 ...

METHOD FOR PRODUCING GAMMA-GLUTAMYL-VALYL-GLYCINE

A microorganism useful as an expression host for γ-Glu-Val synthetase and a method for producing γ-Glu-Val-Gly using γ-Glu-Val synthetase expressed in the microorganism are provided. By using γ-Glu-Val synthetase expressed in a bacterium, such as bacteria, modified so that the activity of a protein encoded by a ybdK gene (YBDK) is reduced as an expression host, γ-Glu-Val-Gly is produced from Glu, Val, and Gly as raw materials. 1. A bacterium ,wherein the bacterium has been modified so that the activity of a protein encoded by a ybdK gene is reduced as compared with a non-modified strain,wherein the bacterium has a gene encoding γ-glutamylvaline synthetase, andwherein the γ-glutamylvaline synthetase shows a ratio of γ-glutamylvaline synthetase activity to γ-glutamylglycine synthetase activity of 3.0 or higher.2. The bacterium according to claim 1 , wherein the protein is a protein defined in (a) claim 1 , (b) claim 1 , or (c) mentioned below:(a) a protein comprising the amino acid sequence of SEQ ID NO: 16;(b) a protein comprising the amino acid sequence of SEQ ID NO: 16 but including substitution, deletion, insertion, or addition of 1 to 10 amino acid residues, and having γ-glutamylglycine synthetase activity;(c) a protein comprising an amino acid sequence showing an identity of 90% or higher to the amino acid sequence of SEQ ID NO: 16, and having γ-glutamylglycine synthetase activity.3. The bacterium according to claim 1 , wherein the activity of the protein is reduced by attenuating the expression of the ybdK gene claim 1 , or by disrupting the ybdK gene.4. The bacterium according to claim 1 , wherein the γ-glutamylvaline synthetase is a protein defined in (a) claim 1 , (b) claim 1 , or (c) mentioned below:(a) a protein comprising the amino acid sequence of SEQ ID NO: 18, 20, or 22;(b) a protein comprising the amino acid sequence of SEQ ID NO: 18, 20, or 22 but including substitution, deletion, insertion, or addition of 1 to 10 amino acid residues, and having γ- ...

AZAHETEROCYCLES AS BIR2 AND/OR BIR3 INHIBITORS

Disclosed are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein R, R, R, m, n and q are described in this application, and methods of using said compounds in the treatment of cancer. 2. The compound of wherein Ris halogen claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of wherein Ris H.4. The compound according to wherein Ris aryl that optionally may be substituted with OR claim 1 , halogen and C-alkyl claim 1 , or a pharmaceutically acceptable salt thereof.5. The compound of wherein Ris phenyl or naphthalenyl claim 4 , or a pharmaceutically acceptable salt thereof.6. The compound according to wherein Ris heteroaryl that optionally may be substituted with C-alkyl claim 1 , or a pharmaceutically acceptable salt thereof.7. The compound of wherein Ris selected from selected from quinolinyl claim 6 , benzo[b]thiophenyl or indolyl.8. The compound according to wherein Ris C-alkyl that optionally may be substituted with ORand aryl claim 1 , or a pharmaceutically acceptable salt thereof.9. The compound of wherein Ris C-alkyl substituted with phenyl claim 8 , or a pharmaceutically acceptable salt thereof.10. The compound of wherein Ris ORand Ris H claim 8 , or a pharmaceutically acceptable salt thereof.11. The compound according to wherein Ris C-cycloalkyl claim 1 , or a pharmaceutically acceptable salt thereof.12. The compound of wherein Ris cyclohexyl or cyclopentyl claim 11 , or a pharmaceutically acceptable salt thereof.13. The compound according to wherein Ris aryl claim 1 , or a pharmaceutically acceptable salt thereof.14. The compound of wherein Ris phenyl.15. The compound according to wherein Ris heterocyclyl claim 1 , or a pharmaceutically acceptable salt thereof.16. The compound of wherein Ris tetrahydropyran.17. The compound according to wherein m is o claim 1 , n is 1 claim 1 , and q is o claim 1 , or a pharmaceutically acceptable salt thereof.18. The compound of wherein Ris H claim 1 , Ris aryl claim 1 , Ris C ...

OFF-THE-SHELF CANCER VACCINES

The present invention relates generally to peptide comprising two or more tumor specific neo open-reading-frame peptides (NOPs), and isolated nucleic acids encoding such peptides, and the uses of these peptides and/or isolated nucleic acids to produce cancer vaccines and the like. With the present invention it becomes possible to provide off-the-shelf cancer vaccines and the like within a short period of time and for potentially 30% of the total population of patients suffering from cancer. 1. A peptide comprising at least two amino acid sequences , wherein each of said amino acid sequence is independently selected from the group consisting of SEQ ID Nos 1 to 4307.2. Peptide according to claim 1 , wherein each of said amino acid sequences is independently selected from the sequences of one group selected from the groups 1 to 1103 as listed in Table 1.3. Peptide according to claim 2 , wherein the number of amino acid sequences selected from the one group selected from the groups 1 to [ . . . ] are (X-Y) sequences claim 2 , wherein X represents the total number of sequences in the selected group and Y represents an integer with a value ranging from 0 to (X−2).4. Peptide according to or claim 2 , wherein the peptide comprises all of the amino acid sequences listed in Table 1 for the selected group.5. Peptide according to any one of to claim 2 , wherein said amino acid sequences are directly adjacent to each other claim 2 , or wherein between said amino acid sequences a linker amino acid sequence may be present claim 2 , preferably wherein between each of said amino acid sequences a linker amino acid sequence is present claim 2 , preferably wherein said linker amino acid sequences claim 2 , independently claim 2 , have a length of 1 claim 2 , 2 claim 2 , 3 claim 2 , 4 or 5 claim 2 , or more amino acids.6. Peptide according to claim 5 , wherein at least one claim 5 , preferably all of the linker amino acid sequences have the amino acid sequence VDD.7. An isolated nucleic ...

DIPEPTIDYL PEPTIDASE-IV INHIBITOR

An excellent peptidyl peptidase-IV inhibitor and the like are provided. A peptide consisting of Val-Pro-X wherein X represents an amino acid residue (except for L-proline residue); the aforementioned X is preferably one selected from a basic amino acid residue, an aliphatic neutral amino acid residue, an amide group-carrying neutral amino acid residue, or an aromatic group-carrying neutral amino acid residue; the aforementioned X is preferably one selected from an alanine residue, a glutamine residue, a methionine residue, an asparagine residue, a glycine residue, a valine residue, a tyrosine residue, a serine residue, and a lysine residue; a dipeptidyl peptidase-IV inhibitor, a blood sugar rise suppressing agent, a vascular endothelial disorder suppressing agent, and an angiotensin converting enzyme inhibitor containing the aforementioned peptide as an active ingredient. 1. A peptide consisting of Val-Pro-X , wherein X represents an amino acid residue (except for L-proline residue).2. The peptide according to wherein X is selected from a basic amino acid residue claim 1 , an aliphatic neutral amino acid residue claim 1 , a hydroxyl group-carrying neutral amino acid residue claim 1 , an amide group-carrying neutral amino acid residue and an aromatic group-carrying neutral amino acid residue.3. The peptide according to wherein X is selected from an alanine residue claim 1 , a glutamine residue claim 1 , a methionine residue claim 1 , an asparagine residue claim 1 , a glycine residue claim 1 , a valine residue claim 1 , a tyrosine residue claim 1 , a serine residue and a lysine residue.5. A dipeptidyl peptidase-IV inhibitor containing a peptide consisting of Val-Pro-X wherein X represents an amino acid residue (except for the L-proline residue) as an active ingredient.6. The dipeptidyl peptidase-IV inhibitor according to wherein X is selected from a basic amino acid residue claim 5 , an aliphatic neutral amino acid residue claim 5 , a hydroxyl group-carrying neutral ...

PEPTIDE MACROCYCLES AGAINST ACINETOBACTER BAUMANNII

The present invention provides compounds of formula (I) 3. The compound according to any of or , wherein:{'sup': 1', '1, 'Xis CRor N,'}{'sup': 2', '12, 'Xis CRor N,'}{'sup': 3', '13, 'Xis CRor N,'}{'sup': 4', '14', '1', '2', '3', '4, 'Xis CRor N, with the proviso that not more than two of X, X, Xand Xare N;'}{'sup': 5', '15, 'Xis CRor N,'}{'sup': 6', '16, 'Xis CRor N,'}{'sup': 7', '17, 'Xis CRor N,'}{'sup': 8', '18', '5', '6', '7', '8, 'Xis CRor N, with the proviso that not more than two of X, X, Xand Xare N;'}{'sup': '1', 'sub': 2', 'm', '2', 'm', '1-7', '1-7', '3-7', '1-7, 'Ris —(CH)-heteroaryl or —(CH)— heterocycloalkyl; wherein heteroaryl is optionally substituted with one or more halo, cyano, C-alkyl, C-haloalkyl, C-cycloalkyl or C-alkoxy; and wherein heterocycloalkyl is partly unsaturated;'}{'sup': 2', '4', '6, 'sub': 1-7', '1-7', '3-7, 'R, Rand Rare each individually selected from hydrogen, C-alkyl, C-haloalkyl, and C-cycloalkyl;'}{'sup': 3', '20', '21', '20', '21', '20', '21, 'sub': 1-7', '2', 'n', '2', 'n', '2', 'n', '2', 'q, 'Ris —C-alkyl, —(CH)—NRR, —(CH)—C(O)NRRor —(CH)—O—(CH)—NRR;'}{'sup': 5', '22', '23', '22', '23, 'sub': 1-7', '1-7', '2', 'o', '2', 'o, 'claim-text': [{'sub': 2', 'o', '2', 'q', '2', 'o', '2', 'o, 'sup': 20', '21', '22', '23', '22', '23, '—(CH)—O—(CH)NRR, —(CH)—NH—C(NH)—NRR, —(CH)—NH—C(O)—NRR,'}, {'sub': 2', 'o', '2', 'o', '2', 'o', '2', 'o, 'sup': '26', '—(CH)—NH—C(O)—OR, —(CH)-heterocycloalkyl, —(CH)-heteroaryl, —(CH)-aryl,'}, {'sub': 1-7', '1-7', '1-7, 'wherein cycloalkyl, heterocycloalkyl, heteroaryl and aryl are optionally substituted by halo, cyano, C-alkyl, C-haloalkyl, C-alkoxy or aryl;'}], 'Ris hydrogen, C-alkyl, hydroxy-C-alkyl, —(CH)—NRR, —(CH)—C(O)—NRR,'}{'sup': 7', '8, 'sub': 1-7', '1-7', '3-7', '1-7, 'Rand Rare each individually selected from hydrogen, C-alkyl, C-haloalkyl, C-cycloalkyl and C-alkoxy;'}{'sup': 11', '12', '13', '14', '15', '16', '24', '25', '24', '25, 'sub': 1-7', '1-7', '1-7', '1-7', '1-7', '2', '3-7, ' ...

ANTI-INFLAMMATORY TRIPEPTIDES

The present invention relates to tripeptide compounds according to the general formula (1) and their use as a medicament, in particular as anti-inflammatory agents. 2. The tripeptide compound according to claim 1 ,wherein in general formula (1):{'sup': 1', 'α', 'α', 'α, 'AAis selected from α-amino acids, N-methyl amino acids and N, N-dimethyl amino acids; and'}{'sup': '2', 'AAis selected from α-aminoisobutyric acid, t-butyl glycine, α-aminoisobutyric acid amide and t-butyl glycine amide,'}orwherein:{'sup': 1', 'α', 'α', 'α, 'AAis selected from α-amino acids, N-methyl amino acids and N, N-dimethyl amino acids; and'}{'sup': 2', 'α', 'α, 'AAis selected from N-methyl amino acids and N-methyl amino acid amides.'}4. The tripeptide compound according to claim 1 , wherein in general formula (1) and/or general formula (2):{'sup': 1', 'α', 'α, 'AAis an N, N-dimethyl amino acid;'}{'sup': 2', 'α, 'AAis an N-methyl amino acid.'}5. The tripeptide compound according to claim 1 , wherein in the definition of AAthe N-methyl amino acids and N claim 1 , N-dimethyl amino acids are selected from the group consisting of N-methyl-1-Nal claim 1 , N claim 1 ,N-dimethyl-1-Nal claim 1 , N-methyl-2-Nal claim 1 , N claim 1 ,N-dimethyl-2-Nal claim 1 , N-methyl-Abu claim 1 , N claim 1 ,N-dimethyl-Abu claim 1 , N-methyl-Ala claim 1 , N claim 1 ,N-dimethyl-Ala claim 1 , N-methyl-Arg claim 1 , N claim 1 ,N-dimethyl-Arg claim 1 , N-methyl-Asn claim 1 , N claim 1 ,N-dimethyl-Asn claim 1 , N-methyl-Cha claim 1 , N claim 1 ,N-dimethyl-Cha claim 1 , N-methyl-Cit claim 1 , N claim 1 ,N-dimethyl-Cit claim 1 , N-methyl-Cys claim 1 , N claim 1 ,N-dimethyl-Cys claim 1 , N-methyl-Dab claim 1 , N claim 1 ,N-dimethyl-Dab claim 1 , N-methyl-Dap claim 1 , N claim 1 ,N-dimethyl-Dap claim 1 , Sar claim 1 , N claim 1 ,N-dimethyl-Gly claim 1 , N-methyl-His claim 1 , N claim 1 ,N-dimethyl-His claim 1 , N-methyl-Hle claim 1 , N claim 1 ,N-dimethyl-Hle claim 1 , N-methyl-Homophe claim 1 , N claim 1 ,N-dimethyl-Homophe ...

Combination therapy for treating hcv infection in an hcv-hiv coinfected patient population

The present invention relates to therapeutic combinations comprising (a) Compound (1), or a pharmaceutically acceptable salt thereof, as herein described, (b) an interferon alfa and (c) ribavirin. Compound (1) is a selective and potent inhibitor of the HCV NS3 serine protease. The present invention also relates to methods of using such therapeutic combinations for treating HCV infection or alleviating one or more symptoms thereof in a patient that is co-infected with HIV.

TRIPEPTIDE EPOXY KETONE PROTEASE INHIBITORS

Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): 260-. (canceled)65. (canceled)68. (canceled)7079-. (canceled)80. A pharmaceutical composition comprising the compound of claim 61 , or pharmaceutically acceptable salt thereof claim 61 , and a pharmaceutically acceptable carrier or diluent.81. A method of inhibiting immunoproteasome of a cell comprising contacting the cell with a compound of in an effective to inhibit the immunoproteasome in the cell.82. The method of claim 81 , wherein the compound inhibits β5i (LMP7).83. The method of claim 82 , wherein the compound further inhibits one or both of LMP2 and MECL-1.8485-. (canceled)86. The method of claim 81 , wherein the contacting comprises administering the compound or the composition to a subject.8789-. (canceled)90. The method of claim 86 , wherein the subject suffers from an autoimmune disease.91. (canceled)92. A method for the treatment of an immune-related disease claim 61 , comprising administering a therapeutically effective amount of the compound of to a subject in need thereof.93. The method of claim 92 , wherein the immune-related disease is rheumatoid arthritis claim 92 , lupus claim 92 , inflammatory bowel disease claim 92 , multiple sclerosis claim 92 , or Crohn's disease.94. A method for the treatment of inflammation claim 61 , comprising administering a therapeutically effective amount of the compound of to a subject in need thereof.95. A method for treating infection claim 61 , comprising administering a therapeutically effective amount of a compound of the compound of to a subject in need thereof.96. A method for treating neurodegenerative disease claim 61 , compromising administering a therapeutically effective amount of the compound of to a subject in need thereof.97. The method of claim 96 , wherein the neurodegenerative ...

Cell-free protein synthesis method and device using a eukaryotic cell lysate in the presence of a caspase inhibitor and the use of a caspase inhibitor for increasing the yield and/or the stability of the synthesized proteins in such a method

The invention relates to an improved cell-free protein synthesis method using a eukaryotic cell lysate in the presence of a caspase inhibitor, to a device for carrying out said method, and to the use of a caspase inhibitor for increasing the protein yield or for increasing the stability of the synthesized proteins in such a cell-free protein synthesis method using a eukaryotic cell lysate. In a preferred embodiment of the invention, the cell-free protein synthesis method is carried out as a continuous method in a device which comprises at least two compartments separated by a dialysis membrane. The translation reaction takes place in at least one first compartment, the reaction compartment, and during the translation reaction i) reactants are diffused from at least one other compartment, the supply and discharge compartment, into the reaction compartment, and ii) reaction byproducts are diffused from the reaction compartment into the supply and discharge compartment by means of the dialysis membrane. According to the invention, the caspase inhibitor is provided at least in the reaction compartment but can also be preferably provided in the supply and discharge compartment in order to supply unused inhibitors to the reaction compartment.

HEMIASTERLIN DERIVATIVES FOR CONJUGATION AND THERAPY

Provided herein are hemiasterlin derivatives, conjugates thereof, compositions comprising the derivatives or conjugates thereof, methods of producing the derivatives and conjugates thereof, and methods of using the derivatives, conjugates, and compositions for the treatment of cell proliferation. The derivatives, conjugates, and compositions are useful in methods of treatment and prevention of cell proliferation and cancer, methods of detection of cell proliferation and cancer, and methods of diagnosis of cell proliferation and cancer. In an embodiment, the hemiasterlin derivatives are according to Formula 1000: 48-. (canceled)10. The compound of claim 9 , wherein Ris methyl claim 9 , ethyl claim 9 , or propyl.11. (canceled)12. (canceled)14. The compound of claim 13 , wherein RT comprises a residue of a natural or non-natural amino acid or a residue of a sugar.16. (canceled)18. The compound of claim 15 , wherein SG comprises C-Calkylene claim 15 , C-Calkylene claim 15 , —C(O)— claim 15 , or a combination thereof.20. (canceled)23. The compound of claim 1 , wherein W claim 1 , W claim 1 , W claim 1 , W claim 1 , and Ware each independently a single bond claim 1 , absent claim 1 , or comprise —C(O)— claim 1 , —O— claim 1 , —C(O)NH— claim 1 , —C(O)NH-alkyl- claim 1 , —OC(O)NH— claim 1 , —SC(O)NH— claim 1 , —NH— claim 1 , —NH-alkyl- claim 1 , —N(CH)CHCHN(CH)— claim 1 , —S— claim 1 , —S—S— claim 1 , —OCHCHO— claim 1 , or a combination thereof.24. The compound of where W claim 2 , W claim 2 , W claim 2 , W claim 2 , and Ware independently absent or a bond; or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or tautomer thereof.25. (canceled)26. The compound of claim 13 , wherein Ar is a divalent six-membered claim 13 , substituted or unsubstituted claim 13 , monocyclic aryl or monocyclic heteroaryl ring.27. (canceled)28. The compound of claim 13 , wherein Ar is a divalent nine-membered claim 13 , substituted or unsubstituted claim 13 , fused bicyclic ...

MBTH-LIKE PROTEINS IN THE PRODUCTION OF SEMI SYNTHETIC ANTIBIOTICS

The present invention relates to the preparation of β-lactam antibiotics comprising contacting 4-hydroxyphenylglycine or phenylglycine, cysteine and valine with a non-ribosomal peptide synthetase and subsequent cyclization using an isopenicillin N synthase in the presence of an MbtH-like protein and to a host cell equipped to perform such preparation. 2. Method according to wherein said MbtH-like protein has SEQ ID NO: 18 claim 1 , SEQ ID NO: 19 claim 1 , SEQ ID NO: 20 claim 1 , SEQ ID NO: 30 claim 1 , SEQ ID NO: 31 or SEQ ID NO: 32 or a sequence that is at least 50% homologous to SEQ ID NO: 18 claim 1 , SEQ ID NO: 19 or SEQ ID NO: 20 claim 1 , SEQ ID NO: 30 claim 1 , SEQ ID NO: 31 or SEQ ID NO: 32.3. Method according to wherein said MbtH-like protein has the amino acid code NXEXQXSXWP-X-PXGW-X-L-X-WTDXRP.4. Method according to wherein said non-ribosomal peptide synthetase comprises a first module M1 specific for 4-hydroxyphenylglycine and/or phenylglycine claim 1 , a second module M2 specific for cysteine and a third module M3 specific for valine.5. Method according to which is carried out in a eukaryotic microorganism.6Penicillium.. Method according to wherein said eukaryotic microorganism is7. Method according to wherein said β-lactam antibiotic is an N-α-aminophenylacetyl β-lactam antibiotic and said first module M1 comprises an adenylation domain chosen from the list consisting of SEQ ID NO: 1 claim 4 , SEQ ID NO: 2 claim 4 , SEQ ID NO: 3 claim 4 , SEQ ID NO: 4 claim 4 , SEQ ID NO: 5 claim 4 , SEQ ID NO: 6 claim 4 , SEQ ID NO: 7 and a sequence that is at least 50% homologous to SEQ ID NO: 1 claim 4 , SEQ ID NO: 2 claim 4 , SEQ ID NO: 3 claim 4 , SEQ ID NO: 4 claim 4 , SEQ ID NO: 5 claim 4 , SEQ ID NO: 6 or SEQ ID NO: 7.8. A eukaryotic host cell comprising a non-ribosomal peptide synthetase claim 4 , an isopenicillin N synthase and a polynucleotide allowing the expression of an MbtH-like protein.9. Host cell according to wherein said MbtH-like protein has SEQ ID ...

ENZYMES FOR TRANSFORMING ERGOPEPTINES AND METHOD THEREFOR

Enzymes for transforming, in particular hydrolytically cleaving, ergopeptines, which ergopeptines are α/β-hydrolases hydrolytically cleaving ergopeptines in the cyclol ring, for the transformation of ergopeptines, and method for producing ergopeptine-metabolizing enzymes. 1. Enzymes for transforming , in particular hydrolytically cleaving , ergopeptines , wherein said enzymes are α/β-hydrolases hydrolytically cleaving ergopeptines in the cyclol ring.2. The enzymes according to claim 1 , wherein said enzymes comprise a catalytic triad consisting of a nucleophilic amino acid claim 1 , of histidine and of an acidic amino acid claim 1 , and that the triad is contained in a peptide chain with an α/β-hydrolase fold.3. The enzymes according to claim 2 , wherein the catalytic triad consists of the nucleophilic amino acid serine claim 2 , of histidine and one of the acidic amino acids claim 2 , aspartate or glutamate claim 2 , and that the triad is contained in a peptide chain with an α/β-hydrolase fold.4. The enzymes according to claim 1 , wherein the α/β-hydrolase comprises a nucleophilic elbow having the sequence Gly-Gln-Ser-Arg-Asn-Gly.5. The enzymes according to claim 1 , wherein they comprise at least 96% sequence identity with a sequence ID No. 1.6. The enzymes according to claim 5 , wherein it is claim 5 , in particular claim 5 , an enzyme having sequence ID No. 3.7. The enzymes according to claim 5 , wherein it is claim 5 , in particular claim 5 , an enzyme having sequence ID No. 1.8. The enzymes according to claim 5 , wherein they comprise a claim 5 , in particular extended claim 5 , N- or C-terminal sequence different from the sequence ID No. 1 claim 5 , in particular an enzyme having sequence ID No. 3 or sequence ID No. 5.9. A method for enzymatically transforming ergopeptines claim 5 , wherein the ergopeptines are hydrolytically cleaved in the cyclol ring to primary metabolites.10. The method according to claim 9 , wherein said cleaving is effected by a ...

PHOTOLABILE LINKER FOR THE SOLID-PHASE SYNTHESIS OF HYDRAZIDES AND PYRANOPYRAZOLES

The photolabile hydrazine linker of the present invention is based on the o-nitro-veratryl group, which is capable of releasing hydrazide derivatives upon UV irradiation. The linker allows for a new solid-phase peptide synthesis (SPPS) strategy which is fully orthogonal to the most commonly used protecting groups and chemical methods in SPPS and shows excellent compatibility with peptide composition, notably the 20 naturally occurring a-amino acid residues (even in their side-chain protected form) are accepted in the C-terminal of the peptide hydrazides. Furthermore, the linker unit can be applied to synthesize combinatorial libraries of biological interesting heterocyclic compounds, such as pyranopyrazoles. 2. The photolabile hydrazine linker according to claim 1 , wherein R* is OH and R is hydrogen or a protecting group.3. The photolabile hydrazine linker according to claim 1 , wherein n is an integer from 2 to 5 claim 1 , or from 3 to 5 or n is 3.5. The protected hydrazine-functionalized photolabile linker according to claim 1 , wherein R* is a connection to a solid support and R is a protecting group.7. A solid support comprising an immobilized protected hydrazine-functionalized photolabile linker according to claim 6 , wherein the connection between the solid support and the hydrazine-functionalized photolabile linker comprises a spacer and/or an orthogonally cleavable linker.10. The solid support according to claim 6 , wherein PG is a protecting group selected from the group comprising Cbz (Z) claim 6 , multiple substituted methoxy- claim 6 , nitro- claim 6 , or chloro Cbz (including Z(4-MeO) claim 6 , Z(2-NO2) claim 6 , Z(4-NO2) claim 6 , Z(2-Cl) claim 6 , Z(3-Cl) claim 6 , Z(2 claim 6 ,4-Cl) claim 6 , Z(3 claim 6 ,5-OMe)) claim 6 , Ddz claim 6 , Nvoc claim 6 , Pz claim 6 , Tmz claim 6 , Bic claim 6 , Bpoc claim 6 , Azoc claim 6 , iNoc Bocm Cyoc claim 6 , Tcboc claim 6 , Adoc claim 6 , Adpoc claim 6 , Iboc claim 6 , Fmoc claim 6 , Tsoc claim 6 , Msc claim 6 , ...

TRIPEPTIDE COMPOUND, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF

Provided are a tripeptide compound, a preparation method therefor, and an application thereof. The structure of the related compound is represented by formula (I). The provided compound has angiotensin converting enzyme inhibiting bioactivity, and the compound and a pharmaceutical composition thereof play a role in preventing and treating hypertension and other cardiocerebral vascular system diseases.

PRODRUG OF AN ICE INHIBITOR

This invention describes an ICE inhibitor prodrug (I) having good bioavailability. 2. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier claim 1 , adjuvant or vehicle.3. A method for treating or preventing a disease selected from an IL-1 mediated disease claim 2 , an apoptosis mediated disease claim 2 , an inflammatory disease claim 2 , an autoimmune disease claim 2 , a destructive bone disorder claim 2 , a proliferative disorder claim 2 , an infectious disease claim 2 , a degenerative disease claim 2 , a necrotic disease claim 2 , an excess dietary alcohol intake disease claim 2 , a viral mediated disease claim 2 , uveitis claim 2 , inflammatory peritonitis claim 2 , osteoarthritis claim 2 , pancreatitis claim 2 , asthma claim 2 , adult respiratory distress syndrome claim 2 , glomerulonephritis claim 2 , rheumatoid arthritis claim 2 , systemic lupus erythematosus claim 2 , scleroderma claim 2 , chronic thyroiditis claim 2 , Grave's disease claim 2 , autoimmune gastritis claim 2 , insulin-dependent diabetes mellitus (Type I) claim 2 , autoimmune hemolytic anemia claim 2 , autoimmune neutropenia claim 2 , thrombocytopenia claim 2 , chronic active hepatitis claim 2 , myasthenia gravis claim 2 , inflammatory bowel disease claim 2 , Crohn's disease claim 2 , psoriasis claim 2 , atopic dermatitis claim 2 , graft vs host disease claim 2 , osteoporosis claim 2 , leukemias and related disorders claim 2 , myelodysplastic syndrome claim 2 , multiple myeloma-related bone disorder claim 2 , acute myelogenous leukemia claim 2 , chronic myelogenous leukemia claim 2 , metastatic melanoma claim 2 , Kaposi's sarcoma claim 2 , multiple myeloma claim 2 , sepsis claim 2 , septic shock claim 2 , Shigellosis claim 2 , Alzheimer's disease claim 2 , Parkinson's disease claim 2 , cerebral ischemia claim 2 , myocardial ischemia claim 2 , myocardial infarction claim 2 , congestive heart failure claim 2 , Huntington's disease claim 2 , ...

NOVEL CHONDRAMIDE DERIVATIVES

The present invention provides novel chondramide derivatives of formula (I) which can be used for the treatment of cancer. 2. A compound according to claim 1 , wherein Ris Br claim 1 , F or Cl.4. A compound according to claim 1 , wherein R1 is a hydrogen atom claim 1 , a hydroxy group or a methoxy group.5. A compound according to claim 1 , wherein R5 is a hydrogen atom or a C1-C8 alkyl group claim 1 , preferably a C1-C8 alkyl group.6. A compound according to claim 1 , wherein Ris a hydrogen atom or a methyl group.7. A compound according to claim 1 , wherein Ris a C-Calkyl group or a group of formula —CH-Ind claim 1 , wherein Ind is an optionally substituted indole group.9. A compound according to claim 1 , wherein Ris a hydrogen atom or a methyl group.10. A compound according to any one of the preceding claim 1 , wherein R9 is a methyl group.111. A compound according to claim claim 1 , wherein R10 is a hydrogen atom or a methyl group.12. A compound according to claim 1 , wherein R claim 1 , Rand Rare independently from each other a hydrogen atom or a methyl group.13. A compound according to claim 1 , wherein R7 and/or R9 is a group of formula —CH2-CH2-CH2-CH2-NH2 or —CH2-CH2-CH2-CH2-NHR71 claim 1 , wherein R71 is fluoresceinyl claim 1 , diacetylated fluoresceinyl claim 1 , rhodaminyl claim 1 , Carboxytetramethylrhodaminyl (TAMRA) claim 1 , BODIPY or a cyanine.14. A pharmaceutical composition comprising a compound according to and optionally one or more carrier substances and/or one or more adjuvants.15. (canceled)16. A compound according to wherein R3 is a hydroxy group.17. A compound according to wherein R1 is a hydrogen atom.18. A compound according to wherein R5 is an ethyl group.19. A compound according to wherein R6 is a hydrogen atom.20. A method for treating a subject suffering from cancer claim 1 , comprising administering to the subject and effective amount of a compound or pharmaceutical composition of . Chondramides A to D are cyclodepsipeptides that were ...

AGENT FOR PREVENTING ARTERIOSCLEROSIS, AGENT FOR SUPPRESSING VASCULAR INTIMAL THICKENING AND AGENT FOR IMPROVING VASCULAR ENDOTHELIAL FUNCTION

Provided is an agent having at least one of an improving effect on vascular endothelial functions and an inhibitory effect on vascular intimal thickening, as well as a prophylactic of arteriosclerosis, which have excellent safety, improve functions associated with the vascular endothelium, have effects of preventing various diseases associated with vascular endothelial functions and of inhibiting vascular intimal thickening, and may be expected to provide prophylactic effect on arteriosclerosis. The agents of the present invention contain, as an active component: (a) Xaa-Pro-Pro, (b) a hydrolysate of animal milk casein containing Xaa-Pro-Pro, or a concentrate thereof, or (c) a fermentation product containing Ile-Pro-Pro and/or Val-Pro-Pro obtained by fermenting a starting material containing milk protein with a bacterial strain of the species 1. A method for inhibiting decrease in vascular endothelial functions and for inhibiting vascular intimal thickening , said method comprising orally administering an effective amount of a hydrolysate of animal milk casein or a concentrate thereof , said hydrolysate comprising a tripeptide Ile-Pro-Pro and/or Val-Pro-Pro , to a subject ,wherein said subject is suffering from impaired endothelial functions and thickened vascular intima, andwherein a content of said tripeptide Ile-Pro-Pro and/or Val-Pro-Pro is not less than 0.3 wt % of the total amount of peptides and free amino acids in the hydrolysate of animal milk casein.2. The method according to claim 1 , wherein said hydrolysate of animal milk casein further comprises a dipeptide Xaa-Pro.3. The method according to claim 2 , wherein said dipeptide Xaa-Pro comprises at least one dipeptide selected from the group consisting of Ile-Pro claim 2 , Glu-Pro claim 2 , Arg-Pro claim 2 , Gln-Pro claim 2 , Met-Pro claim 2 , Tyr-Pro claim 2 , and mixtures thereof.4. The method according to claim 2 , wherein a content of said dipeptide Xaa-Pro is not less than 5 wt % of the total amount ...

INHIBITORS OF NF KAPPA-B ACTIVITY FOR TREATMENT OF DISEASES AND DISORDERS

Peptides and methods of use thereof, are disclosed for use in treating various disease and disorders, including inflammation, pain, oral mucositis, oral lesions, and cancer. The peptides modulate the activity of the transcription 1. A method of treating inflammation in a patient in need thereof , comprising administering to a patient in need thereof a composition comprising a therapeutically effective amount of one or more peptides of four to twenty amino acid residues in length which inhibit the activity of NF kappa B.2. (canceled)3. The method of claim 1 , wherein the one or more peptides are selected from the group consisting of peptides of{'br': None, 'Xxx-Ala-Pro-Glu\u2003\u2003CORE SEQUENCE (1) {'br': None, 'smallcaps': 'D', 'Xxx-Ala-Pro--Glu\u2003\u2003CORE SEQUENCE (2), 'where Xxx is selected from the group consisting of Met, Ile, Val, Cys, Trp, Tyr, Phe, 5-methyl-Trp, allo-Ile, β-styryl-Ala, naphthyl-Ala, diphenyl-Ala, α-aminobutyric acid, α-aminocaproic acid, norleucine, α-amino-2-phenylbutyric acid, α-Amino-1-naphthalenepropanoic acid, β-cyclohexyl-Ala, dehydroalanine, and β-tert-butyl-Ala;'} {'br': None, 'Xxx-Ala-Glu-Ala\u2003\u2003CORE SEQUENCE (3), 'where Xxx is selected from the group consisting of Met, Ile, Val, Cys, Trp, Tyr, Phe, 5-methyl-Trp, allo-Ile, β-styryl-Ala, naphthyl-Ala, diphenyl-Ala, α-aminobutyric acid, α-aminocaproic acid, norleucine, α-amino-2-phenylbutyric acid, α-Amino-1-naphthalenepropanoic acid, β-cyclohexyl-Ala, dehydroalanine, and β-tert-butyl-Ala;'} {'br': None, 'smallcaps': 'D', 'Xxx-Ala--Glu-Ala\u2003\u2003CORE SEQUENCE (4), 'where Xxx is selected from the group consisting of Met, Ile, Val, Cys, Trp, Tyr, Phe, 5-methyl-Trp, allo-Ile, β-styryl-Ala, naphthyl-Ala, diphenyl-Ala, α-aminobutyric acid, α-aminocaproic acid, norleucine, α-amino-2-phenylbutyric acid, α-Amino-1-naphthalenepropanoic acid, β-cyclohexyl-Ala, dehydroalanine, and β-tert-butyl-Ala;'} {'br': None, 'Xxx-Ala-Asn-Ala\u2003\u2003CORE SEQUENCE (5), 'where Xxx is ...

Peptide domains that bind small molecules of industrial significance

Described herein are small peptide domains and consensus sequences that bind small target molecules of industrial importance, e.g., metals such as nickel, β carotene, and isoflavones such as genistein. Also described are fusion proteins containing such binding domains fused to proteins or to peptide domains like GST or CBD that bind other ligands and can be used to immobilize the target binding domain on a support. One class of fusion proteins that is useful in industrial settings are fusions that contain concatemers of target binding domains, which increases the binding equivalents per molecule.

MYOBLAST DIFFERENTIATION PROMOTER

A peptide selected from the group consisting of Ala-Hyp-Gly, Hyp-Gly-Pro, Leu-Hyp, Glu-Hyp, Gly-Pro-Hyp, Pro-Ala, Hyp-Gly and Pro-Hyp, or a pharmaceutically acceptable salt thereof has a myoblast differentiation promoting effect superior to conventional arts. 1. A method for promoting myoblast differentiation promoter comprising administering a peptide selected from the group consisting of Ala-Hyp-Gly , Hyp-Gly-Pro , Leu-Hyp , Glu-Hyp , Gly-Pro-Hyp , Pro-Ala , Hyp-Gly and Pro-Hyp , or a pharmaceutically acceptable salt thereof , to a subject in need thereof.2. The method according to claim 1 , comprising administering a peptide selected from the group consisting of Hyp-Gly and Pro-Hyp claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to a subject in need thereof.3. The method according to claim 1 , comprising administering two or more peptides selected from the group consisting of Ala-Hyp-Gly claim 1 , Hyp-Gly-Pro claim 1 , Leu-Hyp claim 1 , Glu-Hyp claim 1 , Gly-Pro-Hyp claim 1 , Pro-Ala claim 1 , Hyp-Gly and Pro-Hyp claim 1 , or pharmaceutically acceptable salts thereof claim 1 , to a subject in need thereof.4. The method according to claim 1 , wherein the peptide(s) are administered in the form of a preparation for oral administration claim 1 , an injection for direct administration to muscle claim 1 , a transdermal agent claim 1 , a suppository claim 1 , a nasal drop claim 1 , or an inhalant.5. A beverage or food product or a feed claim 1 , comprising a peptide selected from the group consisting of Ala-Hyp-Gly claim 1 , Hyp-Gly-Pro claim 1 , Leu-Hyp claim 1 , Glu-Hyp claim 1 , Gly-Pro-Hyp claim 1 , Pro-Ala claim 1 , Hyp-Gly and Pro-Hyp claim 1 , or a pharmaceutically acceptable salt thereof6. The method according to claim 1 , used for therapy of locomotive syndrome claim 1 , therapy of sarcopenia claim 1 , improvement in the effect of training in athletes claim 1 , students and so on claim 1 , enhancement in physical strength of aged persons ...

Combinatorial Synthesis of Libraries of Macrocyclic Compounds Useful in Drug Discovery

A library of macrocyclic compounds of the formula (I) 16-. (canceled)8. The macrocyclic compound of claim 7 , wherein x claim 7 , y and z are each independently 0 or 1 claim 7 , and X is H. The present application is a continuation application of U.S. patent application Ser. No. 13/218,784, filed Aug. 26, 2011, now allowed, which is a continuation application of U.S. patent application Ser. No. 11/615,332, filed Dec. 22, 2006, now U.S. Pat. No. 8,008,440, which is a continuation application of U.S. patent application Ser. No. 09/679,331, filed Oct. 4, 2000, now U.S. Pat. No. 7,169,899, which claims priority to Canadian Application No. 2,284,459, filed Oct. 4, 1999. The disclosures of each of which are incorporated by reference herein in their entireties.The present invention relates to new macrocyclic compounds of biologically interesting structures. The invention also relates to a process for preparing these new compounds by lactam or Mitsunobu cyclization.As everybody knows, medicinal chemistry research has been dramatically transformed by biotechnology. Previously synthetic chemistry and natural products screening dominated drug research, but now molecular biology has become a driving force behind screening and the establishment of molecular targets.Over the last years, most of the research in biotech companies has been directed to peptide and protein therapeutics in spite of problems associated with their low bioavailability, rapid metabolism, and lack of oral activity. Because of these limitations, research groups continue to rely upon chemical synthesis of nonpeptide substances for drug discovery, recognizing that small molecules are likely to remain the most viable avenue for the identification and optimization of potential drugs.As is also known, combinatorial chemistry is a technique by which large chemical libraries can be generated by connecting together appropriate chemical building blocks in a systematic way. The ability to generate such large, ...

PEPTIDE MACROCYCLES AGAINST ACINETOBACTER BAUMANNII

The present invention provides compounds of formula (I) 151.-. (canceled)5357.-. (canceled)59. (canceled)64. The method of claim 58 , wherein Ris —(CH)-heteroaryl or —(CH)— heterocycloalkyl claim 58 , wherein heteroaryl is monocyclic or bicyclic and is optionally substituted with one or more halo claim 58 , cyano claim 58 , C-alkyl claim 58 , C-haloalkyl claim 58 , C-cycloalkyl or C-alkoxy; and wherein heterocycloalkyl is partly unsaturated.6513. The method of claim 58 , wherein Ris hydrogen claim 58 , C-alkyl claim 58 , hydroxy-C-alkyl claim 58 , —(CH)—NRR claim 58 , —(CH)—C(O)—NRR claim 58 , —(CH)—O—(CH)—NRR claim 58 , —(CH)—NH—C(NH)—NRR claim 58 , —(CH)—NH—C(O)—NRR claim 58 , —(CH)—NH—C(O)—OR claim 58 , —(CH)-heterocycloalkyl claim 58 , —(CH)-heteroaryl claim 58 , —(CH)-aryl claim 58 , wherein heterocycloalkyl claim 58 , heteroaryl and aryl are optionally substituted by halo claim 58 , cyano claim 58 , C-alkyl claim 58 , C-haloalkyl claim 58 , C-alkoxy or aryl; and wherein o claim 58 , q claim 58 , R-Rand Rare as defined in any of claims to .66. The method of claim 58 , wherein Ris hydrogen claim 58 , halo claim 58 , C-alkyl claim 58 , halo-C-alkyl claim 58 , heterocycloalkyl claim 58 , aryl or heteroaryl claim 58 , wherein heteroaryl is optionally substituted with one C-haloalkyl or C-alkoxy.67. The method of claim 58 , wherein Ris hydrogen claim 58 , halo claim 58 , C-alkyl claim 58 , halo-C-alkyl claim 58 , heterocycloalkyl or aryl.68. The method of claim 58 , wherein Ris hydrogen claim 58 , halogen claim 58 , cyano claim 58 , C-alkyl claim 58 , C-haloalkyl claim 58 , —NRR claim 58 , C-alkyl-NRR claim 58 , hydroxy claim 58 , C-alkoxy claim 58 , —B(OH) claim 58 , benzyloxy-propynyl claim 58 , heterocycloalkyl claim 58 , aryl or heteroaryl claim 58 , wherein heterocycloalkyl is optionally substituted with one amino claim 58 , wherein aryl is optionally substituted with one halo claim 58 , cyano claim 58 , —SO—C-alkyl claim 58 , or —SO—NRR claim 58 , and wherein ...

NEW DIFLUOROKETAMIDE DERIVATIVES AS HTRA1 INHIBITORS

The invention provides novel compounds having the general formula (I) 2. A compound according to claim 1 , wherein{'sup': '1', 'sub': '1-6', 'Ris halo-C-alkyl;'}{'sup': '2', 'claim-text': [{'sub': '1-6', 'i) C-alkyl, and'}, {'sub': '3-8', 'ii) C-cycloalkyl;'}], 'Ris selected from'}{'sup': 3', '4', '6', '7', '9', '10', '23, 'R, R, R, R, R, Rand Rare H;'}{'sup': 5', '12', '13', '14, 'Ris phenyl substituted with R, Rand R;'}{'sup': '8', 'claim-text': i) H,', 'ii) hydroxy,', {'sup': 15', '16', '17, 'iii) phenyl substituted with R, Rand R;'}], 'Ris selected from'}{'sup': '11', 'claim-text': [{'sub': '1-6', 'sup': 21', '22, 'i) amino-Cs-alkyl substituted on the nitrogen atom by Rand R,'}, {'sup': 18', '19', '20, 'ii) phenyl substituted with R, Rand R,'}, {'sub': '1-6', 'sup': 18', '19', '20, 'iii) phenyl-C-alkyl substituted with R, Rand R,'}, {'sub': '3-8', 'sup': 18', '19', '20, 'iv) phenyl-C-cycloalkyl substituted with R, Rand R,'}, {'sub': '1-6', 'sup': 18', '19', '20, 'v) phenyl(halo)-C-alkyl substituted with R, Rand R,'}, {'sup': 18', '19', '20, 'vi) heteroaryl substituted with R, Rand R, wherein heteroaryl is selected from pyrazinyl, pyridinyl, pyrimidinyl and thiophenyl,'}], 'Ris selected rom'}{'sup': '12', 'claim-text': i) H, and', {'sub': '1-6', 'ii) C-alkoxy;'}], 'Ris selected from'}{'sup': 13', '14', '17', '20, 'R, R, Rand Rare H;'}{'sup': '15', 'claim-text': [{'sub': '1-6', 'i) C-alkyl,'}, 'ii) cyano,', 'iii) halogen, and', {'sub': '1-6', 'iv) carboxy-C-alkoxy;'}], 'Ris selected from'}{'sup': '16', 'claim-text': i) H, and', 'ii) halogen;, 'Ris selected from'}{'sup': '18', 'claim-text': i) H,', 'ii) halogen,', {'sub': '1-6', 'iii) halo-C-alkoxy,'}, 'iv) cyano,', {'sub': '1-6', 'v) amino substituted on the nitrogen atom by two C-alkyl,'}, {'sub': 1-6', '1-6, 'vi) C-alkoxycarbonyl-C-alkoxy,'}, {'sub': '1-6', 'vii) carboxy-C-alkoxy, and'}, 'viii) morpholinyl;, 'Ris selected from'}{'sup': '19', 'claim-text': i) H and', 'ii) halogen;, 'Ris selected from'}{'sup': '21 ...

INSULIN A-CHAIN DERIVED PEPTIDE FRAGMENT AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DIABETES OR DIABETIC WOUNDS, CONTAINING THE SAME

The present invention relates to an insulin-A-chain-derived peptide fragment and a pharmaceutical composition for the prevention or treatment of diabetes or diabetic wounds, containing the same as an active ingredient. The peptide of the present invention induces endocytosis through an insulin receptor and exhibits activity of enhancing glucose uptake into cells by translocating a glucose transporter to a cell membrane, and of increasing cell migration and proliferation. Therefore, the peptide of the present invention can be efficiently applied to the prevention or treatment of diabetes or diabetic wounds. 1. A peptide comprising three or four amino acids represented by Chemical Formula 1 below:{'br': None, 'X-A-Leu-Y\u2003\u2003'}wherein A is serine (Ser) or glutamine (Gln);X is hydrogen, tyrosine (Tyr) or cysteine (Cys);Y is hydrogen, tyrosine (Tyr) or glutamic acid (Glu);neither X nor Y is hydrogen; and— is a peptide bond.2. The peptide of claim 1 , which is a peptide represented by Chemical Formula 1a below:{'br': None, 'X1-Ser-Leu-Y1\u2003\u2003'}wherein X1 is hydrogen or cysteine (Cys);Y1 is hydrogen or tyrosine (Tyr);neither X1 nor Y1 is hydrogen; and— is a peptide bond.3. The peptide of claim 2 , which is a peptide selected from the group consisting of SEQ ID NOS: 1 claim 2 , 3 claim 2 , and 4.4. The peptide of claim 2 , which is a peptide of SEQ ID NO: 3.5. The peptide of claim 1 , which is a peptide represented by Chemical Formula 1 b below:{'br': None, 'X2-Gln-Leu-Y2\u2003\u2003'}wherein X2 is hydrogen or tyrosine (Tyr);Y2 is hydrogen or glutamic acid (Glu);neither X2 nor Y2 is hydrogen; and— is a peptide bond.6. The peptide of claim 5 , which is a peptide selected from the group consisting of SEQ ID NOS: 2 claim 5 , 5 claim 5 , and 6.7. A pharmaceutical composition for preventing or treating diabetes or diabetic wounds claim 1 , containing claim 1 , as an active ingredient claim 1 , the ...

一种突变酶及其应用和酶催化法制备三胜肽的工艺

本发明涉及生化技术领域，公开了一种突变酶及其应用和酶催化法制备三胜肽的工艺。本发明包括甘氨酸和L‑组氨酸连接酶GHS以及三肽连接酶HKS；或为两者的融合酶。本发明通过改造让Lal酶实现甘氨酸、L‑组氨酸连接酶活力从而获得GHS酶，以及让gshB酶实现二肽甘氨酸‑L‑组氨酸与L‑赖氨酸的合成能力从而获得HKS酶。在此基础上，进一步利用多肽链将GHS酶与HKS酶进行融合，则可以构造一次性连接甘氨酸、L‑组氨酸以及L‑赖氨酸的双功能酶GHKS，从而实现方便的、高收率的制备三胜肽；而对于该酶催化反应中所需要的大量ATP，可以采用多聚磷酸激酶进行循环再生，进而大大降低ATP的用量。

组织再生用材料、含有该组织再生用材料的蛋白质水溶液和使该组织再生用材料凝胶化的方法

本发明的目的在于提供抑制细菌的增殖、并且促进肉芽组织形成或上皮化的组织再生用材料。本发明的组织再生用材料是由人工蛋白聚合物(A)构成的组织再生用材料，其中，(A)具有多肽链(Y)和/或多肽链(Y’)，多肽链(Y)是VPGVG序列(2)、GVGVP序列(3)、GPP序列、GAP序列和GAHGPAGPK序列(4)中的任意1种氨基酸序列(X)连续2～200个而成的多肽链；多肽链(Y’)是(Y)中的1～100个氨基酸被赖氨酸和/或精氨酸取代了的多肽链；(A)中的(Y)与(Y’)的合计个数为1～100个；(A)的疏水度为0.2～1.2。

Patent CH618960A5

Novel substrate for measuring kallikrein in urine

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

Protein aqueous solution

Method of preparing peptides or salts

Method for removing transition metals, particularly from metathesis products

縮合されていてもよく及び／又は置換されていてもよい複素環化合物を添加することを含む、金属錯体を含む溶液中の前記錯体の濃度を下げる方法。添加される化合物は、第二溶液中の前記錯体の溶解性を高める化合物である。その後に、前記錯体を含む溶液を、第二溶液で抽出することができる。

Patent JPH0533718B2

Method for quantitative determination of hydrolytic enzymes

HCV NS3 protease inhibitors

The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

HCV NS3 protease inhibitor

Inhibitory octapeptides angiotensin II

Octapeptide derivatives characterized by an oxygen or sulfur-containing moiety in the C-terminal position are potent inhibitors of the pharmacological effects of Angiotensin and possess the additional advantage of a favorable antagonist/agonist ratio.

Method for synthesizing a cyclic multivalent peptide using a thiol-mediated reaction

A method has been developed for the formation of multivalent cyclic peptides. This procedure exploits on-resin peptide cyclization using a photoinitiated thiol-ene click reaction and subsequent clustering using thiol-yne photochemistry. Both reactions utilize the sulfhydryl group on natural cysteine amino acids to participate in the thiol-mediated reactions.

Method for synthesizing a cyclic multivalent peptide using a thiol-mediated reaction

A method has been developed for the formation of multivalent cyclic peptides. This procedure exploits on-resin peptide cyclization using a photoinitiated thiol-ene click reaction and subsequent clustering using thiol-yne photochemistry. Both reactions utilize the sulfhydryl group on natural cysteine amino acids to participate in the thiol-mediated reactions.

Pharmacological agent for urinary stone disease treatment

FIELD: pharmaceuticals.SUBSTANCE: invention relates to the use of the tripeptide Leu-Ile-Lys (leucine – isoleucine – lysine) as a pharmacological agent for the treatment of urinary stone disease.EFFECT: advantages of the claimed invention are high anti-lithogenic activity.1 cl, 2 tbl, 2 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 679 120 C1 (51) МПК C07K 5/083 (2006.01) A61K 38/06 (2006.01) A61P 13/04 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07K 5/0808 (2018.08); A61K 38/06 (2018.08); A61P 13/04 (2018.08) (21)(22) Заявка: 2018138102, 29.10.2018 (24) Дата начала отсчета срока действия патента: Дата регистрации: Приоритет(ы): (22) Дата подачи заявки: 29.10.2018 (45) Опубликовано: 06.02.2019 Бюл. № 4 Адрес для переписки: 656038, г. Барнаул, пр. Ленина, 40, АГМУ, научное управление (56) Список документов, цитированных в отчете о поиске: RU 2652339 C1, 25.04.2018. US 2 6 7 9 1 2 0 R U (54) Фармакологическое средство для лечения мочекаменной болезни (57) Реферат: Изобретение относится к применению Преимуществами заявленного изобретения трипептида Leu-Ile-Lys (лейцин – изолейцин – являются высокая антилитогенная активность. 2 лизин) в качестве фармакологического средства табл., 2 пр. для лечения мочекаменной болезни. Стр.: 1 C 1 C 1 20100190724 A1, 29.07.2010. 2 6 7 9 1 2 0 (73) Патентообладатель(и): Федеральное государственное бюджетное образовательное учреждение высшего образования "Алтайский государственный медицинский университет" Министерства здравоохранения Российской Федерации (RU) 06.02.2019 R U 29.10.2018 (72) Автор(ы): Жариков Александр Юрьевич (RU), Якушев Николай Николаевич (RU), Жарикова Ганна Викторовна (RU) RUSSIAN FEDERATION (19) RU (11) (13) 2 679 120 C1 (51) Int. Cl. C07K 5/083 (2006.01) A61K 38/06 (2006.01) A61P 13/04 (2006.01) FEDERAL SERVICE FOR INTELLECTUAL PROPERTY (12) ABSTRACT OF INVENTION (52) CPC C07K 5/0808 (2018.08); A61K 38/06 (2018.08); A61P 13/04 (2018.08) (21)(22) ...

Activatable optical molecular probe and preparation method and application thereof

本发明公开了一种用于恶性乳腺癌双模态成像的可激活光学分子探针P及P‑Dex。该分子探针不仅可以区分检测高恶性乳腺癌细胞与预后良好的乳腺癌细胞，还能够实现高恶性、预后差的三阴性乳腺癌的活体近红外荧光、光声定性定量分析诊断。此外，与小分子探针P相比，P‑Dex具有更优异的光学性能和生物相容性，且可以通过肾清除，具有更高的成像应用前景。本发明还提供了所述分子探针的制备方法及成像应用。

Liquid automatic dish washing detergent compositions with stabilised subtilisin

Liquid automatic dish washing detergent compositions with stabilised subtilisin

The stabilization of subtilisins by peptide aldehydes, hydrosulfite adducts thereof or peptide methyl ketones, is particularly effective in liquid ADW detergents which contain a strong sequestering builder.

Peptide acetals for stabilising enzymes

The present invention relates to a compound for stabilizing enzymes, the use of said compound for stabilizing an enzyme, a composition comprising said compound, a method of preparing the composition comprising said compound, a detergent composition comprising said compound and a method of preparing said compound.

NEW ORGANIC COMPOUNDS, THEIR PRODUCTION AND USE

X-Pro structure specific ACE inhibitory peptide and preparation method thereof

本发明公开了一种X‑Pro结构特异型ACE抑制肽及其制备方法，所述制备方法包括采用胰凝乳蛋白酶和脯氨酸特异内切酶复合酶酶解牡蛎蛋白，采用Sephadex G25凝胶过滤层析、Superdex TM 30 Increase 10/300 GL凝胶过滤层析、反相高效液相色谱对牡蛎蛋白水解产物进行分离纯化，得到纯度较高的组分，经鉴定ACE抑制肽的氨基酸序列为Ser‑Ala‑Pro、Ala‑Met‑Pro、Thr‑Ser‑Gly‑Pro和Ser‑Asp‑Pro，这四种肽未曾报道过，为制备治疗高血压的药物提供了新途径。

SUBSTRATES FOR USE IN DETERMINING THE CONCENTRATION OF URINALLIC REIN.

"METHOD FOR PRODUCING COMPOUNDS CONTAINING CARBONIC ACID AMIDE, IN PARTICULAR PEPTIDES"

Patent FR2150146A5

NEW TRIPEPTIDE, PROCESS FOR THE PREPARATION THEREOF AND USE THEREOF

La présente invention concerne un nouvel intermédiaire de synthèse peptidique ayant la composition suivante :Leucyl - Arginyl - Prolineainsi que son procédé de préparation. The present invention relates to a novel peptide synthesis intermediate having the following composition: Leucyl - Arginyl - Prolinea as well as its preparation process.

NEW POLYPEPTIDES, THEIR PREPARATION AND THEIR APPLICATION AS MEDICINAL PRODUCTS

NEW CHROMOGENIC ENZYMATIC SUBSTRATES

NOVEL PEPTIDES CARRYING A FLUOROPHORE, PROCESS FOR THEIR PREPARATION AND THEIR APPLICATION TO FLUORIMETRIC DETERMINATION OF ENDOTOXINS

PEPTIDES, UTILISABLES POUR LE DOSAGE FLUORIMETRIQUE DES ENDOTOXINES, REPONDANT A LA FORMULE GENERALE: (CF DESSIN DANS BOPI) DANS LAQUELLE PEPT- DESIGNE

PROCEDURE FOR REMOVING GROUPS PROTECTING THIOL GROUPS PRESENT IN AMINO ACIDS AND PEPTIDES

Procédé pour enlever des groupements protégeant les groupes thiol présents dans des amino-acides et des peptides. On enlève les groupements protecteurs protégeant les groupes thiols d'un amino-acide ou d'un peptide, groupes thiol protégés par les groupements para-méthoxybenzyle, l-adamantyle ou tertio-butyle, en traitant l'amino-acide ou le peptide protégé avec un sel mercurique de l'acide acétique ou d'un acide halogéno-acétique, l'élimination étant effectuée sélectivement et très doucement avec un bon rendement dans des conditions extrêmement douces, sans qu'il y ait une influence quelconque défavorable sur d'autres groupes fonctionnels ou d'autres groupements protecteurs. Utilisation de ce procédé dans la synthèse de peptides. A method of removing groups protecting thiol groups present in amino acids and peptides. The protective groups protecting the thiol groups of an amino acid or a peptide, thiol groups protected by the para-methoxybenzyl, 1-adamantyl or tert-butyl groups, are removed by treating the amino acid or the protected peptide. with a mercuric salt of acetic acid or of a halo-acetic acid, the removal being carried out selectively and very gently with good yield under extremely mild conditions, without there being any adverse influence on any other functional groups or other protecting groups. Use of this process in the synthesis of peptides.

PROCESS FOR THE PREPARATION OF SOLID PHASE POLYPEPTIDES

NOVEL BIOLOGICALLY ACTIVE SUBSTANCES OBTAINED FROM BOVINE CASEIN, THEIR PREPARATION PROCESS AND THE COMPOSITIONS CONTAINING THEM

L-3- (3,4-DIHYDROXYPHENYL) 2-METHYLALANINE PEPTIDES AND THEIR PREPARATION PROCESS