EPITOPE TAG FOR AFFINITY-BASED APPLICATIONS

Described is an epitope tag useful in affinity-based applications. The invention further includes fusion proteins, methods for preparing fusion proteins, nucleic acid molecules encoding these fusion proteins and recombinant host cells that contain these nucleic acid molecules. The invention also relates to nanobodies and other affinity ligands specifically recognizing the epitope tag, and uses thereof in affinity-based applications. 1. An epitope tag consisting of NO:1.2. A non-naturally occurring fusion protein comprising the epitope tag according to and a target protein.3. The non-naturally occurring fusion protein according to wherein the epitope tag is directly coupled to the C-terminal end of the target protein or via a linker.4. An isolated polynucleotide encoding the epitope tag according to .5. A vector comprising the polynucleotide according to .6. A host cell comprising the polynucleotide according to .7. An affinity ligand that specifically binds to the epitope tag of .8. The affinity ligand according to wherein said affinity ligand is an antibody or an antibody fragment or a nanobody.9. A complex of:(i) an affinity ligand that binds to an epitope tag consisting of SEQ ID NO:1; and{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, '(ii) the non-naturally occurring fusion protein of .'}10. The complex according to wherein said complex is crystalline.11. An affinity-based method selected from the group consisting of affinity chromatography methods claim 9 , affinity purification methods claim 9 , immunoprecipitation methods claim 9 , in vivo imaging methods claim 9 , tandem affinity purification methods claim 9 , protein detection methods claim 9 , immunochemistry methods claim 9 , surface-display methods claim 9 , FRET-type methods claim 9 , and co-crystallization methods claim 9 , wherein the improvement comprises:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'utilizing the epitope tag of in the affinity-based method.'}12. The affinity-based method ...

PEPTIDES FOR THE REGULATION OF NEUROTRANSMITTER SEQUESTRATION AND RELEASE

A method of selecting an agent comprising a neuroprotecting activity is disclosed. The method comprises: 1. A method of selecting an agent comprising a neuroprotecting activity , the method comprising:(a) introducing a plurality of agents into a plurality of cells;(b) analyzing Vesicular Monoamine Transporter 2 (VMAT2) transcription in said cells; and(c) identifying an agent of the plurality of agents capable of up-regulating DJ-1-dependent VMAT2 transcription in said cells, thereby selecting the agent comprising the neuroprotecting activity.2. The method of claim 1 , wherein the agent is a peptide agent.3. The method of claim 1 , wherein the agent is a small molecule.4. The method of claim 2 , wherein said peptide agent comprises a DJ-1 sequence.5. The method of claim 1 , wherein said cell is a neuronal cell.6. The method of claim 5 , wherein said neuronal cell is a neuroblastoma cell.7. The method of claim 1 , wherein said analyzing is effected by determining an interaction between the agent and a promoter region of a Vesicular Monoamine Transporter 2 (VMAT2) polynucleotide.8. The method of claim 1 , wherein said analyzing is effected by a transcription assay.9. The method of claim 8 , wherein said transcription assay is a reporter based assay.10. The method of claim 7 , wherein said promoter region of VMAT2 is endogenous to said cell.11. The method of claim 7 , wherein said promoter region of VMAT2 is exogenous to said cell.12. The method of claim 11 , wherein said promoter region is transcriptionally linked to a detectable polypeptide.13. An agent identified according to the method of .14. The agent of claim 13 , being a peptide agent.15. An isolated peptide or peptide mimetic thereof claim 13 , comprising an amino acid sequence which regulates VMAT2 transcription claim 13 , the peptide being no more than 30 amino acids in length.16. An isolated peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-6 claim 13 , 17-526 and ...

NEUROTROPHIC PEPTIDES

The present invention relates to a neurotrophic peptide having an amino acid sequence of VGDGGLFEKKL (SEQ ID NO:1) and alternatively comprising an adamantyl group at the C- and/or N-terminal end. The neurotrophic peptide can rescue cognition, correct impairments in neural cell proliferation and synaptic plasticity, and thus address the cognitive defects associated with Down syndrome. 1. A method of treating a subject having Down syndrome comprising the step of administering a therapeutic amount of at least a portion of a neurotrophic peptide having the amino acid sequence VGDGGLFEKKL (SEQ ID NO: 1).2. The method of claim 1 , wherein said neurotrophic peptide comprises GDGGLFEK (SEQ ID NO: 5).3. The method of claim 1 , wherein said neurotrophic peptide comprises GLFEKKL (SEQ ID NO: 6).4. The method of claim 1 , wherein said neurotrophic peptide comprises VGDG (SEQ ID NO: 7).5. The method of claim 1 , wherein said neurotrophic peptide comprises GDGG (SEQ ID NO: 8).6. The method of claim 1 , wherein said neurotrophic peptide comprises DGGL (SEQ ID NO: 9).7. The method of claim 1 , wherein said neurotrophic peptide comprises GGLF (SEQ ID NO: 10).8. The method of claim 1 , wherein said neurotrophioc peptide is administered subcutaneously.9. A method of treating a subject having Down syndrome comprising the step of administering a therapeutic amount of at least a portion of a neurotrophic peptide having the amino acid sequence VGDGGLFEKKL (SEQ ID NO: 1) bound to an adamantane building block.10. The method of claim 12 , wherein said adamantane building block is bound to a C-terminus of said neurotrophic peptide.11. The method of claim 12 , wherein another adamantane building block is bound to an N-terminus of said neurotrophic peptide.12. The method of claim 12 , wherein said adamantane building block comprises 3-aminoadamantane-1-carboxylic acid.13. The method of claim 12 , wherein said neurotrophic peptide comprises DGGL (SEQ ID NO: 9).14. The method of claim 12 , ...

QUINOXALINE-CONTAINING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS

The present invention discloses compounds of formula I and II or pharmaceutically acceptable salts, esters, or prodrugs thereof: 1. A compound of Formula I or II:wherein{'sub': 2', '1, 'A is absent or selected from —(C═O)—, —S(O), —C═N—ORor —C(═N—CN);'}{'sub': 201', '1', '8', '2', '8', '2', '8', '1', '8', '2', '8', '2', '8', '3', '12', '3', '12', '3', '12', '3', '12, 'Lis absent or selected from —C-Calkylene, —C-Calkenylene, or —C-Calkynylene each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; substituted —C-Calkylene, substituted —C-Calkenylene, or substituted —C-Calkynylene each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C-Ccycloalkylene, or substituted —C-Ccycloalkylene each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C-Ccycloalkenylene, or substituted —C-Ccycloalkenylene each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N;'}{'sub': 2', '1', '1, 'M is absent or selected from O, S, SO, SOor NR; wherein Ris selected at each occurrence from the group consisting of(i) hydrogen;(ii) aryl; substituted aryl; heteroaryl; substituted heteroaryl;(iii) heterocycloalkyl or substituted heterocycloalkyl;{'sub': 1', '8', '2', '8', '2', '8', '3', '8', '2', '8', '2', '8', '3', '12', '3', '12', '3', '12', '3', '12, '(iv) —C-Calkyl, —C-Calkenyl, or —C-Calkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; substituted —C-Calkyl, substituted —C-Calkenyl, or substituted —C-Calkynyl each containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C-Ccycloalkyl, or substituted —C-Ccycloalkyl; —C-Ccycloalkenyl, or substituted —C-Ccycloalkenyl;'}{'sub': 101', '1', '8', '2', '8', '2', '8', '1', '8', '2', '8', '2', '8', '3', '12', '3', '12', '3', '12', '3', '12, 'Lis absent or selected from —C-Calkylene, —C-Calkenylene, or —C-Calkynylene each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; substituted —C-Calkylene, substituted —C-Calkenylene, or substituted —C-Calkynylene each ...

NEUROTROPHIC PEPTIDES

The present invention relates to a neurotrophic peptide having an amino acid sequence of VGDGGLFEKKL (SEQ ID NO: 1) and alternatively comprising an adamantyl group at the C- and/or N-terminal end. The neurotrophic peptide can rescue cognition, correct impairments in neural cell proliferation and synaptic plasticity, and thus address the cognitive defects associated with Alzheimer's disease. 1. A method of treating a subject having Alzheimer's disease comprising the step of administering a therapeutic amount of at least a portion of a neurotrophic peptide having the amino acid sequence VGDGGLFEKKL (SEQ ID NO: 1).2. The method of claim 1 , wherein said neurotrophic peptide comprises GDGGLFEK (SEQ ID NO: 5).3. The method of claim 1 , wherein said neurotrophic peptide comprises GLFEKKLW (SEQ ID NO: 6).4. The method of claim 1 , wherein said neurotrophic peptide comprises VGDG (SEQ ID NO: 7).5. The method of claim 1 , wherein said neurotrophic peptide comprises GDGG (SEQ ID NO: 8).6. The method of claim 1 , wherein said neurotrophic peptide comprises DGGL (SEQ ID NO: 9).7. The method of claim 1 , wherein said neurotrophic peptide comprises GGLF (SEQ ID NO: 10).8. The method of claim 1 , wherein said neurotrophioc peptide is administered peripherally.9. The method of claim 1 , wherein said neurotrophioc peptide is administered subcutaneously.10. The method of claim 1 , wherein said neurotrophioc peptide is administered orally.11. The method of claim 1 , wherein said neurotrophioc peptide is administered intraperitoneally.12. A method of treating a subject having Alzheimer's disease comprising the step of administering a therapeutic amount of at least a portion of a neurotrophic peptide having the amino acid sequence VGDGGLFEKKL (SEQ ID NO: 1) bound to an adamantane building block.13. The method of claim 12 , wherein said adamantane building block is bound to a C-terminus of said neurotrophic peptide.14. The method of claim 12 , wherein another adamantane building block is ...

BRANCHED CHAIN-CONTAINING AROMATIC COMPOUND

The present invention provides a particular branched chain-containing aromatic compound. The branched chain-containing aromatic compound of the present invention is easily-soluble in isopropyl acetate superior in liquid-separation operability, and can be used for a production method of peptide and the like, which provides a final product simply by extraction separation, without crystallization and isolation of each intermediate in each step. 125-. (canceled)29. A method according to claim 28 , further comprising one or more repetitions of steps (5)-(7):(5) removing the N-terminal protecting group of an obtained N-protected C-protected peptide to obtain a C-protected peptide;(6) condensing an N-protected amino acid or N-protected peptide with the N-terminus of said obtained C-protected peptide to give another N-protected C-protected peptide; and(7) adding water to the reaction system after step (6), and separating an impurity by extraction into an aqueous layer.30. A method according to claim 28 , further comprising one or more repetitions of steps (5)-(7′):(5) removing the N-terminal protecting group of an obtained N-protected C-protected peptide to obtain a C-protected peptide;(6) condensing an N-protected amino acid or N-protected peptide with the N-terminus of said obtained C-protected peptide to give another N-protected C-protected peptide; and(7′) adding a hydrophilic organic solvent to the reaction system after step (6), and separating an impurity by extraction into a hydrophilic organic solvent layer.31. A method of synthesizing an organic compound claim 28 , comprising forming a peptide by a method according to . The present invention relates to an aromatic compound containing a particular branched chain. The present invention further relates to a protecting reagent containing the compound or an adduct thereof. The present invention also relates to a production method of peptide by using the compound, and further relates to an organic synthesis method ...

Neurogenic brain-derived neurotrophic factor peptides

Five tetra peptides corresponding to different active regions of brain derived neurotrophic factor (BDNF) that are neurotrophic and can modulate BDNF signaling in a partial agonist/antagonist way. The peptides offer a therapeutic approach to neural pathologies where BDNF levels are dysregulated.

BRANCHED CHAIN-CONTAINING AROMATIC COMPOUND

The present invention provides a particular branched chain-containing aromatic compound. The branched chain-containing aromatic compound of the present invention is easily-soluble in isopropyl acetate superior in liquid-separation operability, and can be used for a production method of peptide and the like, which provides a final product simply by extraction separation, without crystallization and isolation of each intermediate in each step. 125-. (canceled)2831-. (canceled) The present invention relates to an aromatic compound containing a particular branched chain. The present invention further relates to a protecting reagent containing the compound or an adduct thereof. The present invention also relates to a production method of peptide by using the compound, and further relates to an organic synthesis method including the production method of the peptide.The production methods of peptide are generally divided into solid phase methods and liquid phase methods. The solid phase methods are advantageous since isolation and purification after reaction can be performed by only washing resin. However, they are associated with problems in that the reaction is essentially that of heterogeneous phases, reaction agents and reagents need to be used in excess to compensate for the low reactivity, and tracing of reaction and analysis of reaction product supported by carrier are difficult. On the other hand, the liquid phase method is advantage since it shows good reactivity, and intermediate peptide can be purified by extraction and washing, isolation and the like after condensation reaction. However, the method is associated with problems since the production step is complicated due to an extraction and washing step with a nonpolar organic solvent and an acidic or basic aqueous solution to remove residual reagents and/or byproducts in each step of coupling reaction and deprotection, and/or an isolation and purification step such as crystallization and the like, and the like ...

SOLUTION PHASE SYNTHESIS AND CRYSTALLIZATION OF BETA-TURN PEPTIDOMIMETIC CYCLIC SALTS

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I: 2. The method of wherein the β-turn peptidomimetic cyclic compound of formula (I) has a macrocyclic ring of from 14 to 16 ring atoms.3. The method of wherein Rand Rare independently a side chain substituent of two different amino acids.4. The method of wherein Rand Rare independently a side chain substituent of lysine claim 3 , glutamic acid claim 3 , tyrosine claim 3 , isoleucine claim 3 , asparagine claim 3 , arginine or threonine.5. The method of wherein Rand Rare independently a side chain substitutent of glutamic acid or lysine.6. The method of wherein Rand Rare independently a side chain substitutent of isoleucine or arginine.7. The method of wherein Rand Rare independently selected from the group consisting of trifluoroacetyl claim 1 , formyl claim 1 , acetyl claim 1 , t-butyloxycarbonyl (BOC) claim 1 , cyclohexyloxycarbonyl claim 1 , fluorenyl-9-methoxy-carbonyl (Fmoc) claim 1 , benzyloxycarbonyl (Cbz) claim 1 , Cbz derivatives claim 1 , triphenyl claim 1 , methyl claim 1 , benzyl claim 1 , allyloxycarbonyl claim 1 , tert-butyl claim 1 , alkyl sliane and allyl.8. The method of wherein Ris trityl or tert-butyldimethylsilane (TBDMS).9. The method of wherein Ris a side chain substitutent of glutamic acid and Ris allyl or tert-butyl.10. The method of wherein Ris tert-butyl.11. The method of wherein Ris a side chain substitutent of lysine and Ris benzyloxycarbonyl claim 1 , allyloxycarbonyl claim 1 , or tert-butyloxycarbonyl (BOC).12. The method of wherein Ris tert-butyloxycarbonyl (BOC).13. The method of wherein Rand Rare independently hydrogen or Cto Calkyl.14. The method of wherein R claim 1 , Rand Rare hydrogen.15. The method of wherein Wand Ware independently a side chain substituent of two different amino acids claim 1 , less a hydrogen atom on the functional group.16. The method of wherein Wand Ware independently a side chain ...

COVALENT GRANZYME B INHIBITORS

Covalent Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. A method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided. 3. The compound of claim 1 , or stereoisomer claim 1 , tautomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '4', 'claim-text': (i) hydrogen,', {'sub': 1', '12, '(ii) C-Calkyl,'}, {'sub': 3', '6, '(iii) C-Ccycloalkyl,'}, {'sub': 6', '10, '(iv) C-Caryl, or'}, {'sub': 3', '10, '(v) C-Cheteroaryl; and'}], 'Ris selected from'}{'sub': 5', '10', '10, 'claim-text': [{'sub': 1', '12', '6', '10', '1', '10, '(i) C-Calkyl optionally substituted with C-Caryl, C-Cheteroaryl, amino, or carboxylic acid,'}, {'sub': 1', '10', '1', '6, '(ii) C-Cheteroalkyl optionally substituted with C-Calkyl or carboxylic acid,'}, {'sub': 3', '6', '1', '6', '6', '10', '3', '10, '(iii) C-Ccycloalkyl optionally substituted with C-Calkyl, optionally substituted C-Caryl, optionally substituted C-Cheteroaryl, amino, or carboxylic acid,'}, {'sub': 6', '10', '1', '6', '6', '10', '3', '10, '(iv) C-Caryl optionally substituted with C-Calkyl, optionally substituted C-Caryl, optionally substituted C-Cheteroaryl, amino, or carboxylic acid, or'}, {'sub': 3', '10, '(v) C-Cheteroaryl.'}], 'Ris —C(═O)—R, wherein Ris selected from'}4. The compound of claim 1 , or stereoisomer claim 1 , tautomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , 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;'} ...

PEPTIDE INHIBITING ACTIVITY OF ARYL HYDROCARBON RECEPTOR AND COSMETIC COMPOSITION USING SAME

Disclosed is a peptide and a cosmetic composition using the same. The peptide inhibits the activity of an aryl hydrocarbon receptor (AhR), whereby the peptide may be used to alleviate skin troubles caused by fine dust. 1. A peptide comprising an amino acid sequence of any one of SEQ ID NOs: 1 to 4.2. The peptide of claim 1 , wherein the peptide reduces an activity of an aryl hydrocarbon receptor (AhR).3. The peptide of claim 1 , wherein the peptide is used to alleviate skin troubles caused by fine dust.4. The peptide of claim 3 , wherein the peptide inhibits inflammation caused by fine dust.5. A cosmetic composition comprising a peptide comprising an amino acid sequence of any one of SEQ ID NOs: 1 to 4.6. The cosmetic composition of claim 5 , wherein the cosmetic composition provides an effect of alleviating skin troubles caused by fine dust. This application claims the benefit under 35 U.S.C. section 371, of PCT International Application No.: PCT/KR2020/009499, filed on Jul. 20, 2020, which claims foreign priority to Korean Patent Application No.: KR10-2019-0168700, filed on Dec. 17, 2019, in the Korean Intellectual Property Office, both of which are hereby incorporated by reference in their entireties.The present disclosure relates to a peptide inhibiting the activity of an aryl hydrocarbon receptor (AhR) and a cosmetic composition using the same.Fine dust refers to particles each having a size of less than 10 μm. Recently, the frequency of events in which the concentration of fine dust in the air exceeds the reference control level has been increasing. Such fine dust is mainly composed of carbon particles and is largely attributable to emissions from automobiles and exhaust gas from factories. The carbon particles contained in fine dust combine with organic compounds such as polyaromatic hydrocarbons and easily bind to an aryl hydrocarbon receptor (AhR) in cells, thereby inducing the release of reactive oxygen species and an inflammatory response, which in turn ...

Polymer-based material having covalently bonded enzymatically degradable peptide sequences

A polymer-based material having covalently bonded enzymatically degradable peptide sequences not degradable by the biological and metabolic activity of cells and tissues is disclosed, wherein the peptide sequences are incorporated into the polymer-based material or conjugated to the polymer-based material. The peptide sequence can be part of the three-dimensional or two-dimensional structure of the polymer-based material. A controlled degradation of a covalent bond in the peptide sequence is effected. Use of such polymer-based material for an in vitro production of cell cultures or tissues or organs, for an in vivo stabilization of donated cells, tissues or organs is also disclosed. An adhesive bond between the material and the sample, i.e. cells, tissues, or organs is controlledly degradable without destroying the integrity of the sample.

Peptide Ligand with Antibody Selectivity and the Application Thereof

This invention discloses a peptide ligand with antibody selectivity and the application thereof. The peptide ligand with antibody selectivity comprises peptide ligand consisted of a sequence with 4 to 6 amino acids. The peptide ligand with antibody selectivity is able to bind with the hydrophobic region at the bottom of antibody's Fc region through non-covalent bonding. The mentioned peptide ligand with antibody selectivity can be applied to biochip for antibody oriented immobilization, and the biochip can provide high recognition efficiency to antigen. Besides, the mentioned peptide ligand with antibody selectivity can be applied as antibody purification material for purifying antibody with respective peptide ligand with antibody selectivity. 1. A peptide ligand with antibody selectivity , comprising:a peptide ligand consisted of a sequence with 4 to 6 amino acids, wherein said peptide ligand has a hydrophilic end and a hydrophobic end, wherein said peptide ligand can bind to a fragment crystallizable (Fc) region of an antibody through non-covalent bonding.2. The peptide ligand with antibody selectivity according to claim 1 , wherein said peptide ligand is selected from at least one of the group consisting of the following: EGEW claim 1 , EEGW claim 1 , EELW claim 1 , RRGW claim 1 , EGEGE claim 1 , EGEGW claim 1 , EGELW claim 1 , EEGGW claim 1 , EELLW claim 1 , EELWL claim 1 , EEWLW claim 1 , EGEGW claim 1 , EEGGLW claim 1 , EGEGLW claim 1 , RRGGLW claim 1 , RGRGLW.3. The peptide ligand with antibody selectivity according to claim 1 , wherein said peptide ligand can bind to a bottom region of an antibody through hydrophobic interaction and electrostatic force.4. An antibody oriented immobilization device with peptide ligand with antibody selectivity claim 1 , comprising:a substrate; anda plurality of peptide ligand with antibody selectivity fixed on the surface of the substrate, wherein said peptide ligand with antibody selectivity comprises a peptide ligand ...

FOLATE-TARGETED DIAGNOSTICS AND TREATMENT

Methods of detecting and assessing functionally active folate receptors on tumors and treatment associated with those tumors are described. Also described are methods of selecting ovarian and lung cancer patients for therapy with a folate-vinca conjugate by identifying functionally active folate receptors on the tumors of the patient. Also described are methods and compositions for treating folate receptor expressing epithelial tumors with a folate-vinca conjugate in combination with doxorubicin such as pegylated liposomal doxorubicin in which the tumors include ovarian, endometrial or non-small cell lung cancer tumors, including platinum-resistant ovarian tumors and platinum sensitive ovarian tumors. Also described are methods of treating platinum-resistant ovarian cancer using a folate-targeted drug, in the absence or presence of selecting the patient by identifying functionally active folate receptors on the tumors of the patient. 1. (canceled)2. A method for a medical person to treat to patient with a tumor expressing functionally active folate receptors , the method comprising the step of:prescribing EC 145 to treat a patient assessed by the medical person to be in need of such treatment because the patient has a tumor expressing functionally active isolate receptors.3. The method of wherein the tumor is a lung tumor.4. The method of wherein the lung tumor is a non-small cell carcinoma of the lung.5. The method of wherein the tumor is an ovarian tumor.6. The method Of wherein the ovarian tumor is a platinum-resistant ovarian tumor.7. The method of wherein the tumor is an endometrial tumor.8. The method of wherein the patient has positive tumor status and wherein the tumor status is EC20+ or EC20++.9. The method of wherein EC20++ denotes that about 100 percent of the tumors are folate-receptor positive and EC20+ denotes that about 1 percent to about 99 percent of the tumors are folate-receptor positive.10. The method of wherein the tumor status is EC20++ and ...

COMPOUNDS USEFUL IN THE TREATMENT AND/OR CARE OF THE SKIN AND THEIR COSMETIC OR PHARMACEUTICAL COMPOSITIONS

Compounds of general formula (I): their stereoisomers, mixtures thereof and/or their cosmetically or pharmaceutically acceptable salts, cosmetic and/or pharmaceutical compositions which contain them and their use in medicine, and in the treatment and/or care of the skin, particularly in the aging and photoaging of the skin, and more particularly for the treatment and/or prevention of wrinkles and/or stretch marks. 2. The compound according to claim 1 , wherein AAis selected from the group consisting of -Asp- claim 1 , -Glu- claim 1 , -Asn- and -Gln- claim 1 , AAis selected from the group consisting of -Val- claim 1 , -Leu- claim 1 , -Ile- and -Met- claim 1 , Ris H claim 1 , and AAis -Tyr- or -Trp-.3. The compound according to claim 1 , wherein AAis selected from the group consisting of -Lys- claim 1 , -Gly- and -Asn- claim 1 , AAis selected from the group consisting of -His- claim 1 , -Thr- claim 1 , -Gln- claim 1 , and -Cit- and AAis 4-Abz.4. The compound according to wherein Ris selected from the group consisting of H claim 1 , acetyl claim 1 , lauroyl claim 1 , myristoyl and palmitoyl claim 1 , AAis -L-Asp- claim 1 , AAis -L-Val- and AAis -L-Tyr- claim 1 , Ris H claim 1 , n is 4 and Ris selected from the group consisting of —NRRand —ORwherein Rand Rare independently selected from H claim 1 , methyl claim 1 , ethyl claim 1 , hexyl claim 1 , dodecyl and hexadecyl.5. A cosmetic or pharmaceutical composition which comprises at least one compound of general formula (I) claim 1 , its stereoisomers claim 1 , mixtures thereof and/or its cosmetically or pharmaceutically acceptable salts claim 1 , according to claim 1 , together with at least one cosmetically or pharmaceutically acceptable excipient or adjuvant.6. The composition according to claim 5 , wherein said compound of general formula (I) claim 5 , its stereoisomers claim 5 , mixtures thereof and/or its cosmetically or pharmaceutically acceptable salts claim 5 , is incorporated into a cosmetic or pharmaceutically ...

CYTOTOXIC BENZODIAZEPINE DERIVATIVES

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VI). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. 29-. (canceled)10. The compound of claim 1 , wherein L′ is represented by the following formula:{'br': None, 'sub': 5', 'a', 'b', 'm, '—NR—P—C(═O)—(CRR)-J\u2003\u2003(B1);'}{'br': None, 'sub': 5', 'a', 'b', 'm′, '—NR—P—C(═O)—Cy-(CRR)-J\u2003\u2003(B2);'}{'br': None, 'sub': 5', 'a', 'b', 'm, '—C(═O)—P—NR—(CRR)-J\u2003\u2003(C1), or'}{'br': None, 'sub': 5', 'a', 'b', 'm′, '—C(═O)—P—NR-Cy-(CRR)-J\u2003\u2003(C2)'} J is —COE;', {'sub': a', 'b', '1', '3, 'Rand R, for each occurrence, are each independently —H, (C-C)alkyl or a charged substituent or an ionizable group Q;'}, 'm is an integer from 1 to 6;', 'm′ is 0 or an integer from 1 to 6; and', {'sub': 1', '3', '1', '3', '1', '3, 'Cy is a cyclic alkyl having 5 or 6 ring carbon atoms optionally substituted with halogen, —OH, (C-C)alkyl, (C-C)alkoxy, or halo(C-C)alkyl.'}], 'wherein1112-. (canceled)1418-. (canceled)19. The compound of claim 10 , wherein P is a peptide containing 2 to 5 amino acid residues.20. The compound of claim 19 , wherein P is selected from Gly-Gly-Gly claim 19 , Ala-Val claim 19 , Val-Ala claim 19 , Val-Cit claim 19 , Val-Lys claim 19 , Phe-Lys claim 19 , Lys-Lys claim 19 , Ala-Lys claim 19 , Phe-Cit claim 19 , Leu-Cit claim 19 , Lle-Cit claim 19 , Trp claim 19 , Cit claim 19 , Phe-Ala claim 19 , Phe-N-tosyl-Arg claim 19 , Phe-N-nitro-Arg claim 19 , Phe-Phe-Lys claim 19 , D-Phe-Phe-Lys claim 19 , Gly-Phe-Lys claim 19 , Leu-Ala-Leu claim 19 , Ile-Ala-Leu claim 19 , Val-Ala-Val claim 19 , Ala-Leu-Ala-Leu claim 19 , β-Ala-Leu-Ala-Leu and Gly- ...

PHARMACEUTICALLY RELEVANT AROMATIC-CATIONIC PEPTIDES

The present technology provides peptides, methods of generating the peptides, and pharmaceutically acceptable salts of the peptides. In some embodiments, the peptide is 2′6′-Dmt-D-Arg-Phe-Lys-NHor Phe-D-Arg-Phe-Lys-NH. 5. The process of any one of - , wherein Yis tert-butyloxycarbonyl (Boc); Xat each occurrence is independently hydrogen , allyloxycarbonyl , benzyloxycarbonyl (Cbz) , or 2-chlorobenzyloxycarbonyl; Xat each occurrence is independently hydrogen , allyloxycarbonyl , benzyloxycarbonyl (Cbz) , or 2-chlorobenzyloxycarbonyl; and Xat each occurrence is independently hydrogen , nitro , allyloxycarbonyl , benzyloxycarbonyl (Cbz) , or 2-chlorobenzyloxycarbonyl.10. The process of claim 1 , whereinthe hydrogen source comprises hydrogen gas, formic acid, formate salts, diimide, cyclohexene, cyclohexadiene, or combinations of any two or more thereof; andthe transition metal catalyst comprises Co, Ir, Mo, Ni, Pt, Pd, Rh, Ru, W, or combinations of any two or more thereof.11. The process of claim 10 , wherein the transition metal catalyst comprises a support material.12. The process of claim 11 , wherein the support material comprises carbon claim 11 , carbonate salts claim 11 , silica claim 11 , silicon claim 11 , silicates claim 11 , alumina claim 11 , clay claim 11 , or mixtures of any two or more thereof.13. The process of claim 12 , wherein the transition metal catalyst comprises Pd on carbon or Pd on silicon.14. The process of any one of - claim 12 , further comprising a solvent.15. The process of claim 14 , wherein the solvent comprises methanol (CHOH) claim 14 , ethanol (EtOH) claim 14 , isopropanol (iPrOH) claim 14 , trifluorethanol (TFE) claim 14 , butanol (BuOH) claim 14 , methylene chloride (CHCl) claim 14 , chloroform (CHCl) claim 14 , benzotrifluoride (BTF; PhCF) claim 14 , tetrahydrofuran (THF) claim 14 , 2-methyltetrahydrofuran (2Me-THF) claim 14 , dimethoxyethane (DME) claim 14 , dioxane claim 14 , ethyl acetate claim 14 , isopropyl acetate claim 14 , ...

ANTI-AMYLOID BETA ANTIBODIES BINDING TO A CYCLIC AMYLOID BETA PEPTIDE

The disclosure pertains to epitopes identified in A-beta including conformational epitopes, antibodies thereto and methods of making and using immunogens and antibodies specific thereto. 1. A cyclic compound comprising an A-beta peptide the peptide comprising QKL and up to 8 , 7 or 6 A-beta residues , and a linker , wherein the linker is covalently coupled to the A-beta peptide N-terminus residue and the A-beta C-terminus residue , optionally wherein the A-beta peptide is selected from a peptide having a sequence of any one of SEQ ID NOS: 1-10 , optionally selected from QKLV (SEQ ID NO: 1) , HQKLV (SEQ ID NO: 2) , HQKLVF (SEQ ID NO: 9) and QKLVF (SEQ ID NO: 10)211.-. (canceled)12. An immunogen comprising the cyclic compound of optionally wherein the cyclic compound is coupled to a carrier protein or immunogenicity enhancing agent claim 1 , optionaly wherein the carrier protein is bovine serum albumin (BSA) or the immunogenicity-enhancing agent is keyhole limpet haemocyanin (KLH).1314.-. (canceled)15. A composition comprising the compound of or an immunogen comprising said compound.16. The composition of claim 15 , further comprising an adjuvant claim 15 , optionally wherein the adjuvant is aluminum phosphate or aluminum hydroxide.17. (canceled)18. An isolated antibody that specifically binds to an A-beta peptide having a sequence of QKLV (SEQ ID NO: 1) or a related epitope sequence claim 15 , optionally as set forth in any one of SEQ ID NOS: 1-10.19. (canceled)20. The antibody of claim 18 , wherein the epitope comprises or consists of QKLV (SEQ ID NO: 1) claim 18 , HQKLV (SEQ ID NO: 2) claim 18 , HQKLVF (SEQ ID NO: 9) or QKLVF (SEQ ID NO: 101.21. (canceled)22. The antibody of claim 18 , wherein the antibody selectively binds A-beta oligomer over A-beta monomer and/or A-beta fibril claim 18 , optionally wherein the selectivity is at least 3 fold claim 18 , at least 5 fold claim 18 , at least 10 fold claim 18 , at least 20 fold claim 18 , at least 30 fold claim 18 , ...

Carbonic anhydrase ix inhibitor conjugates and uses thereof

The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors as therapeutics and imaging agents. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in imaging methods and cancer therapy.

CASPASE-3-TRIGGERED MOLECULAR SELF-ASSEMBLING PET PROBES AND USES THEREOF

Embodiments of the synthesis, radiolabeling and biological applications of an activatable tracer that undergoes intramolecular cyclization and aggregation upon activation by cleavage of a blocking moiety are provided. The probes of the disclosure allow for target-controlled self-assembly of small molecules in living subjects for imaging and drug delivery. The aggregated nanoprobes of the disclosure may be detectable optically, by PET detection, magnetic resonance imaging, and the like depending on the detectable reporter attached to the nanoprobe. 3. The compound of claim 1 , wherein X is a phenyl group.4. The compound of claim 1 , wherein Y is a pyrimidine nitrile group.6. The compound of claim 1 , wherein Ris selected from a fluorescent dye claim 1 , a positron emission tomography (PET) detectable moiety claim 1 , and a magnetic resonance detectable moiety.7. The compound of claim 1 , wherein the fluorescent dye is a cyanine dye.8. The compound of claim 7 , wherein the cyanine dye is Cy5 or Cy5.5.9. The compound of claim 6 , wherein the PET detectable moiety is an F-labelled moiety.10. The compound of claim 6 , wherein the magnetic resonance detectable moiety is a gadolinium ion claim 6 , and wherein the gadolinium ion is attached to the scaffold by a metal chelating group.11. The compound of claim 1 , wherein Ris a peptide having the amino acid sequence Aspartate-Glutamate-Valine-Aspartate (DEVD) and is specifically cleavable from the scaffold by caspase 3/7 claim 1 , a peptide having the amino acid sequence Isoleucine-Glutamate-Phenylalanine-Aspartate (IEFD) or the amino acid sequence Isoleucine-Glutamate-Proline-Aspartate (IEPD) and specifically cleavable from the scaffold by granzyme-B claim 1 , a β-galactosidase-cleavable-moiety claim 1 , or methionine.12. The compound of claim 3 , wherein Ris a glycoside specifically cleavable from the scaffold by β-galactosidase.13. The compound of claim 1 , wherein Ris (CH)—CH claim 1 , wherein m=0-6.16. The compound of ...

ACTIVE PEPTIDE FOR INHIBITING AMPA RECEPTOR AND PREPARATION METHOD AND USE THEREOF

Provided is an active peptide for inhibiting an AMPA receptor and a preparation method and use thereof. The method for preparing the active peptide comprises the following steps: 1) soaking a salmon skin and crushing, adding water and beating, and then adjusting pH to 6.5-7.5; 2) subjecting to a first enzymolysis using a neutral protease; 3) subjecting to a second enzymolysis using papain enzyme and then inactivating enzyme; and 4) centrifuging the enzymatic hydrolysate, and then subjecting the centrifuged supernatant to membrane filtration, concentration and decoloration, to prepare the active peptide. The active peptide contains a tetrapeptide with an amino-acid sequence of Glu-Gly-Ala-Arg. The tetrapeptide has good solubility, can selectively inhibit neuronal synaptic transmission caused by an AMPA receptor, and has a significant antiepileptic effect. 1. A method for preparing an active peptide , comprising the following steps:1) soaking a salmon skin and crushing, adding water and beating, and then adjusting pH to 6.5-7.5, to obtain a slurry;2) subjecting the slurry to a first enzymolysis by using a neutral protease, to obtain a first enzymatic hydrolysate;3) subjecting the first enzymatic hydrolysate to a second enzymolysis by using papain enzyme and then inactivating enzyme, to botain a second enzymatic hydrolysate; and4) centrifuging the second enzymatic hydrolysate, and then subjecting the centrifuged supernatant to membrane filtration, concentration and decoloration, to prepare the active peptide;wherin the active peptide contains a tetrapeptide with an amino-acid sequence of Glu-Gly-Ala-Arg.2. The method according to claim 1 , wherein an alkaline solution with a mass content of 0.1-0.5% is used to soak the salmon skin claim 1 , a mass/volume ratio of the salmon skin to the alkaline solution is controlled to 1:(2-4) claim 1 , and soaking time is 5-20 h.3. The method according to claim 1 , wherein the amount of the neutral protease is 50-500 U/g claim 1 , ...

Galactose Cluster-Pharmacokinetic Modulator Targeting Moiety for siRNA

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers. 2. The composition of wherein Rcomprises cholesterol.3. The composition of wherein Rcomprises hexadec-8-enoyl.4. The composition of wherein Rcomprises oleyl.5. The composition of wherein Rcomprises (9E claim 1 ,12E)-octadeca-9 claim 1 ,12-dienoyl.6. The composition of wherein Rcomprises dioctanoyl.7. The composition of wherein Rcomprises C16-C20 acyl.8. The composition of wherein Rcomprises C16 acyl.9. The composition of wherein Rcomprises C18 acyl.10. The composition of wherein Rcomprises C80 acyl.11. The composition of wherein R3 comprises: galactosamine claim 1 , N-formylgalactosamine claim 1 , N-acetylgalactosamine claim 1 , N-propionyl-galactosamine claim 1 , N-n-butanoylgalactosamine claim 1 , or N-iso-butanoylgalactosamine.12. The composition of wherein RN-formyl-galactosamine.13. The composition of wherein RN-acetylgalactosamine.14. The composition of wherein RN-propionyl-galactosamine.15. The composition of wherein RN-n-butanoyl-galactosamine.16. The composition of wherein RN-iso-butanoylgalactosamine.17. The composition of wherein the composition further comprises a polynucleotide delivery polymer.18. The composition of wherein the polynucleotide delivery polymer comprises a reversibly modified membrane active polyamine.19. The composition of wherein Rcomprises: DNA claim 1 , RNA claim 1 , dsRNA claim 1 , siRNA claim 1 , or miRNA.20. The composition of wherein Rcomprises siRNA. The delivery of polynucleotide and other substantially cell membrane impermeable compounds into a living cell is highly restricted by the complex membrane system of the cell. Drugs used in ...

Process For Extraction Of Peptides And Its Application In Liquid Phase Peptide Synthesis

A process for extraction of a peptide from a reaction mixture resulting from a peptide coupling reaction, the reaction mixture containing the peptide and a polar aprotic solvent selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide and N-methyl-2-pyrrolidone, whereby the process includes a step a) and a step b): step a) including the addition of a component a1) and a component a2), whereby component a1) is 2-methyltetrahydrofuran and component a2) is water, to the reaction mixture, so that a biphasic system with an organic layer and an aqueous layer is obtained; step b) including the subsequent separation of the organic layer containing the peptide from the aqueous layer. In an embodiment, a combination of 2-methyltetrahydrofuran and an organic solvent 1 selected from the group consisting of n-heptane, toluene, ethylacetate, isopropylacetate, acetonitrile and tetrahydrofuran is used for the process for extraction. The extraction step is preferably used in a process for preparation of a peptide in liquid phase.

ACID-CLEAVABLE LINKERS EXHIBITING ALTERED RATES OF ACID HYDROLYSIS

An acid-cleavable peptide linker comprising aspartic acid and proline residues is disclosed. The acid-cleavable peptide linker provides an altered sensitivity to acid-hydrolytic release of peptides of interest from fusion peptides of the formula PEP1-L-PEP2. The inventive linker, L, is described in various embodiments, each of which provides substantially more rapid acid-release of peptides of interest than does a single aspartic acid-proline pair. In an additional aspect, a method of increasing the stability of an acid cleavable linkage to acid hydrolysis is also provided. 1. A method of preparing at least one peptide of interest (“POI”) from a fusion peptide comprising at least one POI , comprising:{'claim-ref': {'@idref': 'CLM-00021', 'claim 21'}, 'a) providing a recombinant cell synthesizing the fusion peptide of'}b) contacting the fusion peptide with a solution of sufficiently acidic pH so that linker L is cleaved, andc) isolating the at least one POI.2. (canceled)3. The method of wherein the recombinant cell is a recombinant microbial cell.4. The method of wherein the recombinant microbial cell is a recombinant yeast cell.5. The method of wherein the recombinant microbial cell is a recombinant bacterial cell.6. The method of wherein the acid-cleavable linker is cleaved by incubating the fusion peptides at a pH in the range from about pH 1 to about pH 4.7. The method of wherein the acid-cleavable linker is cleaved by incubating the fusion peptides at a pH in the range from about pH 2 to about pH 4.8. The method of wherein the acid-cleavable linker is cleaved by incubating the fusion peptides at a pH in the range from about pH 3 to about pH 4.9. The method of wherein the acid-cleavable linker is cleaved by incubating the fusion peptides at a pH of about 4.10. The method of wherein the acid-cleavable linker is cleaved by incubating the fusion peptides at a temperature of about 40° C. to about 90° C.11. The method of wherein the acid-cleavable linker is cleaved by ...

N-CARBOXYALKYL-AURISTATIN AND USE THEREOF

The present application relates to new derivatives of monomethylauristatin F, substituted on the N terminus by a carboxyalkyl group, processes for preparing these derivatives, their use for the treatment and/or prevention of diseases and to produce medication for the treatment and/or prevention of diseases, particularly hyperproliferative and/or angiogenic disorders such as cancer disorders, for example. Such treatments can occur as monotherapies or in combination with other medication or further therapeutic measures. 6. Compound as defined in to for treatment and/or prevention of diseases.7. Compound as defined in one of the to for use in a procedure to treat and/or prevent cancer and tumor diseases.8. Use of a compound as defined in one of the to for production of drug to treat and/or prevent cancer and tumor diseases.9. Drug which contains a compound as defined in one of the to , in combination with one or more inert , non-toxic , pharmaceutically suitable agents.10. Drug which contains a compound as defined in one of the to , in combination with one or more substances.11. Drug as per or for treatment and/or prevention of cancer and tumor diseases.12. Method for treatment and/or prevention of cancer and tumor diseases in humans or animals using an effective amount of at least one compound as defined in one of the to , or of a drug as defined in one of the to . The present application relates to new derivatives of monomethylauristatin F, substituted on the N terminus by a carboxyalkyl group, processes for preparing these derivatives, their use for the treatment and/or prevention of diseases and to produce medication for the treatment and/or prevention of diseases, particularly hyper proliferative and/or antigenic disorders such as cancer disorders, for example. Such treatments can occur as monotherapies or in combination with other medication or further therapeutic measures.Cancer disorders are the result of uncontrolled cell growths in a wide variety of tissues. ...

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 any one of - , wherein M is CH.5. The compound according to any one of - , wherein said ring nitrogen atom is further substituted with a group R , thereby forming a quaternary nitrogen atom and wherein the positive charge associated with the quaternary nitrogen atom is balanced by a pharmaceutically acceptable anion.6. The compound of claim 5 , wherein Ris:{'sub': '2', 'sup': '15', '(i) —CHOC(═O)R;'}{'sub': '2', 'sup': '15', '(ii) —C(═O)OCHOC(═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', '1', '6', '1', '6, 'Ris Calkyl, Chaloalkyl, CalkoxyCalkyl, Caryl, Caralkyl, Ccycloalkyl, heteroaryl including from 5-10 ring atoms (wherein from 1-3 of the ring atoms are independently selected from N, NH, N—C-Calkyl, O, and S), or heterocyclyl including from 3-7 ring atoms (wherein from 1-2 of the ring atoms are independently selected from N, NH, N—C-Calkyl, and O), each of which is optionally substituted; or'}{'sup': '15', 'sub': 'n', 'Ris Y—Z; wherein{'sub': 6-10', '1', '6, 'Y is a divalent spacer comprising one or more of the following moieties (e.g., comprise 1, 2, 3, 4, or 5 of the following moieties; e.g., comprise 1, 2, or 3 of the following moieties; e.g., consist of 1, 2, 3, 4, or 5 of the following moieties; e.g., consist of 1, 2, or 3 of the following moieties): heteroatom (e.g., N, O, or S), alkylene chain, heteroalkylene chain, Carylene, heteroarylene from 5-10 ring atoms (wherein from 1-3 of the ring atoms are independently selected from N, NH, N—C-Calkyl, O, and S), polyheteroalkylene chain, alkenylene chain, —OC(═O)—, —C(═O)O—, —NHC(═O)—, —C(═O)NH—, —C(═O)—, cyclodextrin, human serum ...

METHOD OF ENHANCING A BRAIN OR COGNITIVE FUNCTION

A composition for improving memory, learning ability, and cognitive ability and a method of enhancing a brain or cognitive function by administering the composition to a subject in need thereof. It has been confirmed that a peptide having a C-terminal region ended to GAG had an effect of improving the memory. In order for the peptide to have the effect, it has been confirmed that the peptide should be a peptide of which the length consists of at least 4 amino acids. Further, it has been confirmed that a peptide of which the length of the peptide having the C-terminal region ended to GAG consists of 5 to 9 amino acids has the same effect. As a result, the peptide of the present invention can be used as the composition for improving memory, learning ability, and cognitive ability, and the method of enhancing a brain or cognitive function. 1. A method of enhancing a brain or cognitive function in a subject in need thereof , comprising administering a peptide consisting of SEQ ID NO: 4 (QGAG) , SEQ ID NO:5 (GGAG) , SEQ ID NO:8 (SGGAG) , or SEQ ID NO:9 (GAGGAGGAG) to the subject.2Fasciola hepatica. The method of claim 1 , wherein the subject suffers from a memory claim 1 , cognitive claim 1 , or learning disorder caused by aging claim 1 , Alzheimer's disease claim 1 , schizophrenia claim 1 , Parkinson's disease claim 1 , Huntington's disease claim 1 , pick disease claim 1 , Creutzfeldt-Jakob disease claim 1 , depression claim 1 , head injury claim 1 , stroke claim 1 , CNS hypoxia claim 1 , cerebral ischemia claim 1 , encephalitis claim 1 , forgetfulness claim 1 , traumatic brain injury claim 1 , hypoglycaemia claim 1 , Wernicke-Korsakoff syndrome claim 1 , drug addiction claim 1 , epilepsy claim 1 , claim 1 , hippocampal sclerosis claim 1 , headache claim 1 , brain aging claim 1 , dementia claim 1 , frontotemporal lobar degeneration claim 1 , tumor claim 1 , normal pressure hydrocephalus claim 1 , HIV claim 1 , cerebrovascular disease claim 1 , cerebral disease claim 1 , ...

Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions

The disclosure pertains to methods of treating or preventing a disease or condition associated with and/or induced by soluble A-beta oligomer such as Alzheimer's disease by administering to a subject in need thereof conformation specific and/or selective antibodies or binding fragments thereof and related products. 1. A method of treating or preventing a disease or condition associated with and/or induced by soluble A-beta oligomer comprising administering to a subject in need thereof: an isolated conformation specific and/or selective antibody or binding fragment thereof that specifically and/or selectively binds to a cyclic compound comprising an A-beta peptide having a sequence of QKL , HQK , KLV , HHQK (SEQ ID NO: 1) , QKLV (SEQ ID NO: 5) or HDSG (SEQ ID NO: 9) , they cyclic compound optionally having a sequence of SEQ ID NO: 2 , 3 , 4 , 6 , 7 , 8 , 10 , 11 or 12; an immunogen comprising a cyclic compound comprising an A-beta peptide having a sequence of QKL , HQK , KLV , HHQK (SEQ ID NO: 1) , QKLV (SEQ ID NO: 5) or HDSG (SEQ ID NO: 9); a cell expressing said antibody or binding fragment thereof; or a nucleic acid encoding said antibody or binding fragment thereof.2. The method of claim 1 , wherein the cyclic compound that is specifically and/or selectively bound has a sequence of SEQ ID NO: 2 claim 1 , 6 or 10.3. The method of claim 1 , wherein the antibody or binding fragment selectively binds to the cyclic compound cover a corresponding linear peptide and/or selectively binds A-beta oligomer over A-beta monomer and/or A-beta fibril claim 1 , wherein the antibody is at least 2 fold claim 1 , 3 fold claim 1 , at least 5 fold claim 1 , at least 10 fold claim 1 , at least 20 fold claim 1 , at least 30 fold claim 1 , at least 40 fold claim 1 , at least 50 fold claim 1 , at least 100 fold claim 1 , at least 500 fold claim 1 , at least 1000 fold more selective for the cyclic compound over the corresponding linear compound.4. The method of wherein the antibody or ...

METHOD OF ENHANCING A BRAIN OR COGNITIVE FUNCTION

There is provided a composition for improving memory, learning ability, and cognitive ability and a method of enhancing a brain or cognitive function by administering the composition to a subject in need thereof. It has been confirmed that a peptide having a C-terminal region ended to GAG had an effect of improving the memory. In order for the peptide to have the effect, it has been confirmed that the peptide should be a peptide of which the length consists of at least 4 amino acids. Further, it has been confirmed that a peptide of which the length of the peptide having the C-terminal region ended to GAG consists of 5 to 9 amino acids has the same effect. As a result, the peptide of the present invention can be used as the composition for improving memory, learning ability, and cognitive ability, and the method of enhancing a brain or cognitive function. 1. A method of enhancing a brain or cognitive function in a subject in need thereof , comprising administering a peptide to the subject , wherein the peptide consists of 4 to 9 amino acid residues and the peptide has amino acid sequence SEQ ID NO: 2 (GAG) at its C-terminus , wherein brain or cognitive function is enhanced in said subject.2. The method of claim 1 , wherein the peptide has amino acid sequence of SEQ ID NO: 3 claim 1 , SEQ ID NO: 4 claim 1 , or SEQ ID NO:5 at its C-terminus.3. The method of claim 1 , wherein claim 1 , in addition to SEQ ID NO: 2 claim 1 , the peptide has at least one amino acid residue selected from the group consisting of A claim 1 , G claim 1 , S claim 1 , and Q.4. The method of claim 1 , the peptide has an amino acid sequence consisting of SEQ ID NO: 3 claim 1 , SEQ ID NO: 4 claim 1 , SEQ ID NO:5 claim 1 , SEQ ID NO:6 claim 1 , SEQ ID NO:7 claim 1 , SEQ ID NO:8 claim 1 , or SEQ ID NO:9.5. The method of claim 1 , wherein the subject suffers from a memory claim 1 , cognitive claim 1 , or learning disorder caused by aging claim 1 , Alzheimer's disease claim 1 , schizophrenia claim 1 , ...

Novel peptide and use thereof

The present invention provides a peptide consisting of the amino acid sequence of SEQ ID NO:1 or the amino acid sequence of SEQ ID NO:2, or a pharmaceutically acceptable salt thereof and a use thereof. The present invention can inhibit the entry of beta-amyloid into the brain. In addition, the present invention can be applied more easily with respect to the suppression of the intracerebral action of beta-amyloid and thus is advantageous in having excellent applicability.

TOLL-LIKE RECEPTOR 4 (TLR4) INHIBITORS AND USE THEREOF

Peptides, peptidomimetics and small molecules, collectively referred to as “decoy peptides”, are provided, which interfere with binding to a TIR domain of a toll-like receptor 4 (TLR4), and inhibit a TLR4-induced signaling pathway. These decoy peptides may be useful for treating diseases associated with induction of TLR4 signaling pathway such as a disease or disorder secondary to a cardiovascular disease, sepsis or an inflammatory disease. 2. The compound of claim 1 , wherein the alkyl is a lower alkyl having 1 to 6 or 1 to 4 carbon atoms; the alkenyl and alkynyl are medium size alkenyl and alkynyl having 2 to 10 or 2 to 8 carbon atoms; the cycloalkyl is a saturated claim 1 , all-carbon monocyclic or polycyclic (fused ring) group claim 1 , having 3 to 8 carbon atoms; the aryl is an all-carbon claim 1 , non-saturated monocyclic or polycyclic (fused-ring) group having 6 to 18 claim 1 , carbon atoms; the heteroaryl is a non-saturated monocyclic or polycyclic (fused ring) group having in the ring(s) one or more heteroatoms selected from nitrogen claim 1 , oxygen and sulfur; and the heteroalicyclyl is a monocyclic or polycyclic group having in the ring(s) one or more heteroatoms selected from nitrogen claim 1 , oxygen and sulfur and claim 1 , optionally claim 1 , one or more double bonds.3. The compound of claim 1 , wherein the alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , cycloalkyl claim 1 , aryl and heteroalicyclyl is substituted by one or more groups selected from the group consisting of: S claim 1 , N claim 1 , alkyl claim 1 , mono- claim 1 , di- or tri-haloalkyl claim 1 , —O—(C-C)alkyl claim 1 , —O—(C-C)cycloalkyl claim 1 , hydroxyalkyl claim 1 , (C-C)cycloalkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , aryl claim 1 , heteroaryl claim 1 , heteroalicyclic claim 1 , halo claim 1 , OH claim 1 , O-aryl claim 1 , —SH claim 1 , —S—(C-C)alkyl claim 1 , —S—(C-C)cycloalkyl claim 1 , —S-aryl claim 1 , —O—S═O claim 1 , —S(═O)—R′ claim 1 , —CN claim 1 , —NO claim 1 ...

SAPOSIN-A DERIVED PEPTIDES AND USES THEREOF

Disclosed herein are polypeptides and fusion polypeptides that have anti-angiogenic activity that can be used to inhibit tumor growth and tumor metastasis. The polypeptide consists of or less consecutive amino acid residues (e.g., or ) comprising the active core amino acid sequence DWLP, or an amino acid substitution variant thereof. Specific amino acid substitutions are disclosed herein. In some embodiments, the peptide consists essentially of - mers identified as exhibiting the activity of prosaposin A. Also disclosed herein are therapeutic compositions comprising the polypeptides and fusion polypeptides, and their use in the treatment, prevention, and inhibition of angiogenesis-related diseases and disorders such as cancer and cancer metastasis. 157.-. (canceled)58. An isolated peptide consisting of an amino acid sequence selected from the group consisting of CDWLPK (SEQ ID NO: 3) and DWLPK (SEQ ID NO: 4) , wherein the peptide is acylated , carboxyamidated , pegylated , or conjugated to a polymer that enhances serum half-life of the peptide.59. A chimeric peptide comprising at least a first portion and at least a second portion claim 58 , wherein the first portion is the peptide of and wherein the second portion is a non-Psap polypeptide.60. The chimeric peptide of claim 59 , wherein the second portion comprises an amino acid sequence or a polymer that enhances the serum half-life of said first portion.61. The chimeric peptide of claim 60 , wherein the second portion comprises an antibody Fc domain.62. The chimeric peptide of claim 59 , wherein the second portion comprises an antibody.63. A composition comprising the peptide of and a pharmaceutically acceptable carrier.64. A method of inhibiting angiogenesis in a subject in need thereof claim 63 , the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition of .65. The method of claim 64 , wherein the subject in need thereof has an angiogenesis dependent ...

PEPTIDE

A novel substance which adds body to a food product, and a body-adding agent for food products that uses said substance are provided. More specifically, the body adding agent for food products is characterized by having as an active component a peptide, or a salt thereof, that is characterized in that the γ-glutamyl bond number is 2-4 and the peptide chain length is the γ-glutamyl bond number +1 to +2, a food product manufacturing method that uses said peptide, and a method for adding body to a food product, characterized by adding said peptide are provided. 1. A body taste-imparting agent for a food , comprising a peptide having a γ-glutamyl bond number of 2 to 4 and a peptide chain length of γ-glutamyl bond number +1 to +2 , or a salt thereof , as an active ingredient.2. The body taste-imparting agent according to claim 1 , wherein all γ-glutamyl bonds are continuous from N-terminus of the peptide.3. The body taste-imparting agent according to claim 2 , wherein C-terminus of the peptide is an amino acid or amino acid derivative which binds to glutamic acid with γ-glutamyl bond.4. A body taste-imparting agent for a food claim 2 , comprising one or two or more peptides selected from the group consisting of a peptide consisting of γ-Glu-γ-Glu-X (X is an amino acid or amino acid derivative claim 2 , the same shall apply hereinafter) claim 2 , a peptide consisting of γ-Glu-γ-Glu-γ-Glu-X claim 2 , and a peptide consisting of γ-Glu-γ-Glu-γ-Glu-γ-Glu-X claim 2 , or a salt thereof claim 2 , as an active ingredient.5. The body taste-imparting agent according to claim 4 , wherein X is selected from the group consisting of Tyr claim 4 , Ala claim 4 , Glu claim 4 , Gln claim 4 , Asp claim 4 , Asn claim 4 , Arg claim 4 , His claim 4 , Ile claim 4 , Leu claim 4 , Phe claim 4 , Ser claim 4 , and Val.6. A method for producing a food claim 4 , comprising adding a peptide having a γ-glutamyl bond number of 2 to 4 and a peptide chain length of γ-glutamyl bond number +1 to +2 claim 4 ...

CYTOKININ SYNTHASE ENZYMES, CONSTRUCTS, AND RELATED METHODS

The present disclosure relates to a new class of cytokinin biosynthetic enzymes, cytokinin synthases, which have two domains: an isopentenyl transfer (IPT)-like domain and a cytokinin nucleotide phosphoribohydrolase (PRH)-like domain. The invention provides compositions and methods for the recombinant production of cytokinin synthase, host cells and transformants that include the cytokinin synthases, as well as compositions and formulations that include the disclosed cytokinin synthase. 1. A recombinant polynucleotide comprising{'sub': 2', '1', '2', '3', '4', '5', '6', '3', '4', '5', '6', '7', '8', '7', '8', '9', '10', '9', '10, 'a. a cytokinin synthase coding sequence having at least 57% amino acid sequence identity to any one of SEQ ID NO:3 (EfCKS), SEQ ID NO:9 (AtCKS), SEQ ID NO:13 (BoCKS), SEQ ID NO:17 (IrCKS), SEQ ID NO:21 (AhCKS), or SEQ ID NO:25 (FfCKS), wherein the encoded cytokinin synthase comprises a sequence that, when aligned with a consensus sequence of SEQ ID NO:3 (EfCKS), SEQ ID NO:9 (AtCKS), SEQ ID NO:13 (BoCKS), SEQ ID NO:17 (IrCKS), SEQ ID NO:21 (AhCKS), or SEQ ID NO:25 (FfCKS), comprises (i) a first motif GPTXaa1XaaGKT (SEQ ID NO:30), wherein Xaais G or A and Xaais V, S, A, or T, at consensus sequence amino acid positions 13-20; (ii) a second motif PXaaXaaXaaGGSXaaS (SEQ ID NO:31), wherein Xaais I or V, Xaais L or V, Xaais V or C, and Xaais T or I, at consensus sequence amino acid positions 96-104, (iii) a third motif XaaXaaYGGG (SEQ ID NO:32), wherein Xaais L or I, and Xaais V or I, at consensus sequence amino acid positions 333-338, and (iv) XaaGGYGT XaaEEL (SEQ ID NO:33), where Xaais S or P and Xaais L or M, at consensus sequence amino acid positions 426-438, and'}b. a heterologous sequence.2. The polynucleotide of claim 1 , wherein the cytokinin synthase coding sequence (i) comprises a sequence having at least 70% nucleotide sequence identity to one of SEQ ID NO:1 (EfCKS) claim 1 , SEQ ID NO:8 (AtCKS) claim 1 , SEQ ID NO:12 (BoCKS) claim 1 , ...

DERIVATIVES OF PYRIDINONE AS INHIBITORS FOR TISSUE TRANSGLUTAMINASE

The invention relates to pyridinone derivatives of general formula (I) as inhibitors of tissue transglutaminase, to methods for producing the pyridinone derivatives, to pharmaceutical compositions containing said pyridinone derivatives and to their use for the prophylaxis and treatment of diseases associated with tissue transglutaminase. 114-. (canceled)16. The compound of claim 15 , wherein{'sub': 3', '2', '3', '3', '2', '2, 'Z is —OCH, —OCHCH, —OCH(CH), or —OCH-Ph;'}{'sub': '3', 'R* is —H or —CH; and'}{'sup': '#', 'R represents —NHY.'}22. The compound of selected from the group consisting of:(S,E)-ethyl 6-(benzyloxycarbonylamino)-7-oxo-7-(2-oxo-1-(2-oxo-2-(2,4,6-trimethylphenethylamino)ethyl)-1,2-dihydropyridin-3-ylamino)hept-2-enoate,(S,E)-ethyl 6-(benzyloxycarbonylamino)-7-(1-(2-(isopentylamino)-2-oxoethyl)-6-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate,(S,E)-ethyl 6-(benzyloxycarbonylamino)-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate,(S,E)-ethyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-6-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate,3-(2-(3-((S,E)-2-(benzyloxycarbonylamino)-7-ethoxy-7-oxohept-5-enamido)-6-methyl-2-oxopyridin-1(2H)-yl)acetamido)-5-methylhexanoic acid,(S,E)-isopropyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-di-hydropyridin-3-ylamino)-7-oxohept-2-enoate,(S,E)-ethyl 6-acetamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate,(S,E)-ethyl 7-(6-methyl-2-oxo-1-(2-oxo-2-(phenethylamino)ethyl)-1,2-dihydropyridin-3-ylamino)-6-(nicotinamido)-7-oxohept-2-enoate,(S,E)-ethyl 6-((4-chlorophenyl)methylsulfonamido)-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate,(S,E)-ethyl 6-benzamido-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-ylamino)-7-oxohept-2-enoate,(S,E)-ethyl 6-(furan-3-carboxamido)-7-(1-(2-(isopentylamino)-2-oxoethyl)-2-oxo-1,2- ...

Bioactive polypeptide DELQ and preparation method as well as application thereof

A milk-derived bioactive polypeptide has in vitro antioxidant activity and an immunity-enhancing function, and an amino acid sequence thereof is DELQ. According to in vitro antioxidant and in vitro immunity-enhancing experiments, it is proved that the peptide has good antioxidant activity and promotes immune system activity. 110-. (canceled)11. A bioactive polypeptide , wherein an amino acid sequence thereof is Asp-Glu-Leu-Gln , the bioactive polypeptide is milk-derived.12. The bioactive polypeptide claim 11 , as recited in claim 11 , wherein a nucleotide fragment thereof is encoded.13. The bioactive polypeptide claim 12 , as recited in claim 12 , wherein a sequence of the nucleotide fragment is illustrated as SEQ ID NO: 2.14. A preparation method of a bioactive polypeptide as recited in claim 11 , comprising steps of:{'i': Lactobacillus helveticus', 'Lactobacillus helveticus, '1) fermenting: adding CICC6024 into skim milk for anaerobic fermentation, in such a manner that fermented milk is obtained;'}{'i': 'Lactobacillus helveticus', '2) coarsely extracting the polypeptide: centrifugally separating the fermented milk obtained in the step 1) with a low temperature, and collecting supernatant; and'}3) purifying the polypeptide, comprising steps of:a) ultrafiltering the supernatant obtained in the step 2), and collecting filtrate; andb) separating the filtrate collected by reversed phase high-performance liquid chromatogram separation through a reversed phase chromatographic column SOURSE 5 RPC ST, and collecting a bioactive polypeptide DELQ.15. The preparation method claim 14 , as recited in claim 14 , wherein in the step 1) claim 14 , conditions of the anaerobic fermentation are: a fermentation temperature of 36-38° C. and a fermentation time of 15-20 h.16. The preparation method claim 14 , as recited in claim 14 , wherein in the step a) of the step 3) claim 14 , molecular weight cut-offs of filter membranes for ultrafiltering are respectively 10 kDa and 3 kDa; ...

SOLUTION PHASE SYNTHESIS AND CRYSTALLIZATION OF BETA-TURN PEPTIDOMIMETIC CYCLIC SALTS

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I: 2. The method of wherein the β-turn peptidomimetic cyclic compound of formula (I) has a macrocyclic ring of from 14 to 16 ring atoms.3. The method of wherein Rand Rare independently a side chain substituent of two different amino acids.4. The method of wherein Rand Rare independently a side chain substituent of lysine claim 3 , glutamic acid claim 3 , tyrosine claim 3 , isoleucine claim 3 , asparagine claim 3 , arginine or threonine.5. The method of wherein Rand Rare independently a side chain substitutent of glutamic acid claim 1 , lysine claim 1 , isoleucine or arginine.6. (canceled)7. The method of wherein Rand Rare independently selected from the group consisting of trifluoroacetyl claim 1 , formyl claim 1 , acetyl claim 1 , t-butyloxycarbonyl (BOC) claim 1 , cyclohexyloxycarbonyl claim 1 , fluorenyl-9-methoxy-carbonyl (Fmoc) claim 1 , benzyloxycarbonyl (Cbz) claim 1 , Cbz derivatives claim 1 , triphenyl claim 1 , methyl claim 1 , benzyl claim 1 , allyloxycarbonyl claim 1 , tert-butyl claim 1 , alkyl sliane and allyl.8. The method of wherein Ris trityl or tert-butyldimethylsilane (TBDMS).915-. (canceled)16. The method of wherein Wand Ware independently a side chain substituent of lysine claim 1 , glutamic acid claim 1 , tyrosine claim 1 , isoleucine claim 1 , asparagine claim 1 , arginine or threonine claim 1 , less a hydrogen atom on the functional group.1720-. (canceled)21. The method of wherein X is O claim 1 , S or NH.2225-. (canceled)26. The method of wherein Y is —NO.2729-. (canceled)30. The method of wherein the cyclizing is performed in the presence of a base comprising t-BuOK claim 1 , CsCO claim 1 , KCO claim 1 , or mixtures thereof claim 1 , further wherein the cyclizing is performed in a polar aprotic solvent comprises acetonitrile claim 1 , tetrahydrofurane claim 1 , dioxanes claim 1 , or mixtures thereof.3133-. (canceled)34. The ...

ARTIFICIAL PEPTIDES AND USE THEREOF FOR GLYCOGEN STORAGE DISORDERS

The present invention discloses a peptide capable of stabilizing mutation-induced GBE1 protein destabilization, conjugates comprising same and uses thereof for the treatment of diseases and disorders associate with glycogen storage. 1. An artificial peptide consisting of amino acid sequence Leu-Thr-Lys-Glu (SEQ ID NO:1).2. (canceled)3. A conjugate comprising the peptide of and a moiety linked thereto claim 1 , wherein the moiety is selected from the group consisting of a fluorescent probe claim 1 , a photosensitizer claim 1 , a chelating agent and a therapeutic agent.4. The conjugate of claim 3 , wherein the moiety is linked to the peptide via a spacer claim 3 , and wherein the spacer is selected from the group consisting of a natural or non-natural amino acid claim 3 , a short peptide having no more than 8 amino acids and a C-Calkyl.5. The conjugate of claim 4 , wherein said moiety is a fluorescent probe.6. The conjugate of claim 5 , wherein said fluorescent probe is BPheide taurine amide (BTA) claim 5 , fluorenyl isothiocyanate (FITC) claim 5 , dansyl claim 5 , rhodamine claim 5 , eosin or erythrosine.718-. (canceled)19. A method of treating a disease or disorder associated with glycogen storage in a subject in need thereof claim 5 , the method comprising administering to said subject a pharmaceutical composition comprising an artificial peptide comprising the amino acid sequence set forth in SEQ ID NO: 1.20. The method of claim 19 , wherein the artificial peptide is consisting of the amino acid sequence set forth in SEQ ID NO: 1.21. The method of claim 19 , wherein the disease or disorder is glycogen storage disorder type IV (GSDIV) or the late-onset adult polyglucosan body disease (APBD).22. The method of claim 19 , wherein the pharmaceutical composition further comprises a moiety claim 19 , the moiety being linked to the artificial peptide thereby forming a conjugate therewith claim 19 , wherein the moiety is selected from the group consisting of a fluorescent ...

PRO-SUBSTRATES FOR LIVE CELL APPLICATIONS

Provided are pro-substrates useful in assays of living cells. The pro-substrates can be used to detect the presence or absence of enzymes, such as luciferase, in living cells. The pro-substrates can be coelenterazine derivatives or analogues. 2. (canceled)3. (canceled)5. (canceled)7. (canceled)9. The compound of claim 1 , wherein Ris furylmethyl or benzyl claim 1 , Ris benzyl claim 1 , or Ris hydrogen.1012.-. (canceled)20. A method for detecting a luminescent enzyme in a sample claim 1 , the method comprising claim 1 ,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) contacting the sample with the compound of ; and'}(b) detecting luminescence in the sample,wherein the detection of luminescence indicates the presence of a luminescent enzyme.21. (canceled)22. The method of claim 20 , wherein the sample comprises a cell.23. The method of claim 22 , wherein the cell comprises the luminescent enzyme or expresses the luminescent enzyme.24. (canceled)25. The method of claim 20 , wherein the compound is in a buffered solution.26. The method of claim 25 , wherein the compound is at least partially hydrolyzed to release a cell permeable substrate prior to contact with the sample.27. The method of claim 26 , wherein the buffered solution has a pH that tunes or facilitates self-based catalysis of the compound to release the cell permeable substrate claim 26 , comprises a nucleophile solution claim 26 , wherein the nucleophile solution comprises a nucleophile configured to react with a compound of formula (I) to release the cell permeable substrate claim 26 , or comprises a non-luminescent enzyme that cleaves the cell impermeable moiety of the compound of formula (I) to release the cell permeable substrate.28. (canceled)29. (canceled)30. The method of claim 20 , wherein step (a) further comprises contacting the sample with a nucleophile or non-luminescent enzyme configured to react with a compound of formula (I) to provide a cell permeable substrate.32. (canceled)33. A ...

COMPOSITION FOR IMPROVING MEMORY, LEARNING ABILITY, AND COGNITIVE ABILITY

There is provided a composition for improving memory, learning ability, and cognitive ability. It has been confirmed that a peptide having a C-terminal region ended to GAG had an effect of improving the memory. In order for the peptide to have the effect, it has been confirmed that the peptide should be a peptide of which the length consists of at least 4 amino acids. Further, it has been confirmed that a peptide of which the length of the peptide having the C-terminal region ended to GAG consists of 5 to 9 amino acids has the same effect. As a result, the peptide of the present invention can be used as the composition for improving memory, learning ability, and cognitive ability. 1. (canceled)2. (canceled)3. (canceled)4. A peptide comprising an amino acid sequence having a C-terminal region of GAG , wherein the amino acid sequence of the peptide is GGAG.5. A peptide comprising an amino acid sequence having a C-terminal region of GAG , wherein the amino acid sequence of the peptide is AGAG.6. A peptide comprising an amino acid sequence having a C-terminal region of GAG , wherein the amino acid sequence of the peptide is QGAG.7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled) This application is based on and claim priority from Korean Patent Application No. 10-2015-018011, filed on Dec. 21, 2015, with the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference.The present invention relates to a composition for improving memory, learning ability, and cognitive ability.The brain has various functions, but the most important function is memory and cognition. If there are no cognitive and memory abilities in the human, it is difficult to perform everyday life and it becomes a problem for survival. The memory and cognition are associated with almost all functions of the brain and brain structures associated with the ...

METHOD AND KIT FOR DETECTING BACTERIAL INFECTION

The invention relates to a novel antibody which binds to C-SLPI selected from the group consisting of SEQ ID NOs: and 1. An immunogen comprising a polypeptide hapten comprising the structure Gln-Cys-Leu-Arg (SEQ ID NO: 10) linked to an immunogenicity conferring carrier molecule.221-. (canceled)22. An antibody , or antigen binding fragment thereof , that is capable of binding , optionally specifically binding , to an epitope of C-SLPI , the epitope comprising SEQ ID NO: 6.2334-. (canceled)35. A method of determining susceptibility to , diagnosis of , and/or progression of a disease state , the method comprising determining an individual's C-SLPI level.3638-. (canceled) The instant application claims the benefit of priority under 35 USC §119 to United Kingdom Application No. 1414079.2, entitled “Method and Kit for Detecting Bacterial Infection” filed 8 Aug., 2014 and United Kingdom Application No. 1509564.9, entitled “Method and Kit for Detecting Bacterial Infection” filed 2 Jun., 2015 the entire contents of each of which are incorporated herein by reference in their entirety.The present invention relates to detecting C-SLPI, a C-terminal fragment of SLPI (Secretory leukocyte protease inhibitor). Specifically, the invention describes novel immunogens, novel antibodies, kits and methods for detecting C-SLPI and their use in disease research, diagnosis and treatment.BACKGROUNDChronic lung diseases such as Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disease (COPD) are often associated with chronic bacterial infection (Gibson et al. 2013). This chronic bacterial infection is due to these patients having a highly compromised innate immune system that prevents the body from clearing infections from the lung, in turn leading to an increased, detrimental inflammatory response and remodelling of the lung tissue (Voynow et al. 2008). One such bacterium that is linked with chronic infection in both CF and COPD patients is ; once established, this bacterium is almost ...

Peptidomimetic inhibitors of the peptidyl-prolyl cis/trans isomerase (pin1)

Disclosed are compounds which inhibit Pin1 activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysregulated Pin1 activity.

Compositions and methods for the treatment of systemic inflammatory response syndromes

Described herein are peptides from secretory phospholipase A 2 -IB and antibodies that can be used to reduce the contribution of the gastrointestinal tract to inflammatory processes including systemic inflammatory responses. Specifically, antibodies that bind specifically a peptide from secretory phospholipase A 2 -IB prevent death in a mouse model of LPS-induced endotoxemia. The antibodies described herein are particularly useful to treat systemic inflammatory response syndromes, including sepsis.

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.

SELECTIVE INHIBITORS OF PROTEINASE 3

The present invention relates to peptidyl phosphonate esters compounds and their use selective inhibitors of proteinase 3, in particular for treating or diagnosing inflammator autoimmune and cancer disorders. More specifically, the invention concerns nov peptidyl phosphonate esters compounds, including without limitation, compounds with Asp-Tyr-Asp-Ala or Pro-Tyr-Asp-Ala, Pro-Tyr-Asp-Avl, Val-Tyr-Asp-Avl peptide structure or their derivatives. 2. The peptidyl phosphonate ester compound of claim 1 , wherein Z and Zare selected from the group consisting of phenyl claim 1 , phenyl substituted with J claim 1 , and phenyl disubstituted with J.3. The peptidyl phosphonate ester compound of claim 1 , wherein R is selected from the group consisting of: (i) a non-polar aliphatic group or aryl group and their esters claim 1 , ethers or polyethers; (ii) one or more hydrophobic amino acids selected from the group consisting of alanine claim 1 , isoleucine claim 1 , leucine claim 1 , methionine claim 1 , phenylalanine claim 1 , proline claim 1 , tryptophane and valine; and claim 1 , (iii) glycine.4. The peptidyl phosphonate ester compound of claim 1 , wherein Xaa4 is proline.5. The peptidyl phosphonate ester compound of claim 1 , wherein Xaa3 is tyrosine.6. The peptidyl phosphonate ester compound of claim 1 , wherein Xaa2 is aspartic acid.7. The peptidyl phosphonate ester compound of claim 1 , wherein Xaa1 is alanine claim 1 , valine or norvaline.8. The peptidyl phosphonate ester compound of claim 1 , wherein Z and Z1 are 4-chlorophenyl.9. The peptidyl phosphonate ester compound of claim 1 , which is selected from the group consisting of:{'sup': 'P', 'sub': 6', '4', '2, 'i. Ac-Asp-Tyr-Asp-Ala(O—CH-4-Cl);'}{'sup': 'P', 'sub': 6', '4', '2, 'ii. Ac-Pro-Tyr-Asp-Ala(O—CH-4-Cl);'}{'sup': 'P', 'sub': 6', '4', '2, 'iii. Biotin-Asp-Tyr-Asp-Ala(O—CH-4-Cl);'}{'sup': 'P', 'sub': 6', '4', '2, 'iv. Biotin-Pro-Tyr-Asp-Ala(O—CH-4-Cl);'}{'sup': 'P', 'sub': 6', '4', '2, 'v. Biotin-Pro-Tyr-Asp-Avl( ...

PRODRUGS OF PEPTIDE EPOXY KETONE PROTEASE INHIBITORS

This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors. 2. (canceled)4. The compound according to claim 1 , wherein M is CH.59.-. (canceled)10. The compound according to claim 1 , wherein Rand Rare each independently Calkyl claim 1 , and Rand Rare each independently Caralkyl.11. The compound according to claim 1 , wherein Rand Rare both isobutyl claim 1 , Ris phenylethyl claim 1 , and Ris phenylmethyl.1238.-. (canceled)38. The compound of claim 1 ,wherein{'sup': '14', 'Ris{'sub': '2', 'sup': '18', '(i) —CHOC(═O)R;'}{'sub': '2', 'sup': '18', '(ii) —C(═O)OCHOC(═O)R; or'}{'sup': '18', '(iii) —SR;'} [{'sup': '18', 'sub': 1-6', '1-6', '1-6', '6-10', '7-12', '3-7', '1', '6', '1', '6, 'Ris Calkyl, CalkoxyCalkyl, Caryl, Caralkyl, Ccycloalkyl, heteroaryl including from 5-10 ring atoms wherein from 1-3 of the ring atoms are independently selected from N, NH, N—C-Calkyl, O, and S; or heterocyclyl including from 3-7 ring atoms wherein from 1-2 of the ring atoms are independently selected from N, NH, N—C-Calkyl, and O; each of which is optionally substituted; or'}, {'sup': '18', 'sub': 'r', 'Ris —Y′″—Z′″; wherein, 'Y′″ is a divalent spacer comprising one or more of the following moieties: heteroatom, alkylene chain, heteroalkylene chain, polyheteroalkylene chain, alkenylene chain, —OC(═O)—, —C(═O)O—, —NHC(═O)—, —C(═O)NH—, —C(═O)—, cyclodextrin, human serum albumin, amino acid, amino acid mimetic, or hydrazine;', {'sub': '2', 'Z′″ comprises one or more of the following moieties: alkylene chain, heteroalkylene chain, polyheteroalkylene chain, alkenylene chain, cyclodextrin, alkylated cyclodextrin, human serum albumin, —OC(═O)—, —C(═O)O—, —NHC(═O)—, —C(═O)NH—, —C(═O)—, monoclonal anti-body, quaternary ammonium ion, NH, docosahexenoic acid, hyaluronic acid, poly(L-glutamic acid), N-(2-hydroxypropyl) methacrylamide copolymer, or a dendrimer; and'}, 'r is 0 or 1., 'wherein3950.-. (canceled)51. A compound having the formula (SM)-PEG claim 1 ...

Tetrapeptide compound and method for producing same

The present invention is to provide a method for the efficient production on an industrial scale of SS-31 (D-Arg-Dmt-Lys-Phe-NH 2 ), which is an SS peptide. According to the present invention, the desired SS-31 is produced by efficiently synthesizing a tetrapeptide compound as a precursor of SS-31 and improving the tetrapeptide purity by crystallization.

LINEAR PEPTIDE ANTIBIOTICS

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. The compounds provided herein can in other embodiments overcome the resistance conferred by single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases) and in other embodiments provide for a broad spectrum of antibiotic bioactivity. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided. 3. The compound of wherein Ris a bond.6. The compound of wherein n is 1 and p is 0.11. The compound of wherein n is 0.12. The compound of wherein Ris a bond.16. The compound of wherein q is 1; and Ris a bond.18. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.19. A method of treatment of a bacterial infection in a mammal claim 1 , comprising administering an effective amount of a compound of to the mammal at a frequency and for a duration sufficient to provide a beneficial effect to the mammal.20Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus ...

CYTOTOXIC BENZODIAZEPINE DERIVATIVES

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VI). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. 1124-. (canceled)128. The compound of claim 125 , wherein P is a peptide containing 2 to 5 amino acid residues.129. The compound of claim 128 , wherein P is selected from Gly-Gly-Gly claim 128 , Ala-Val claim 128 , Val-Ala claim 128 , Val-Cit claim 128 , Val-Lys claim 128 , Phe-Lys claim 128 , Lys-Lys claim 128 , Ala-Lys claim 128 , Phe-Cit claim 128 , Leu-Cit claim 128 , Lle-Cit claim 128 , Trp claim 128 , Cit claim 128 , Phe-Ala claim 128 , Phe-N-tosyl-Arg claim 128 , Phe-N-nitro-Arg claim 128 , Phe-Phe-Lys claim 128 , D-Phe-Phe-Lys claim 128 , Gly-Phe-Lys claim 128 , Leu-Ala-Leu claim 128 , Ile-Ala-Leu claim 128 , Val-Ala-Val claim 128 , Ala-Leu-Ala-Leu claim 128 , β-Ala-Leu-Ala-Leu and Gly-Phe-Leu-Gly claim 128 , Val-Arg claim 128 , Arg-Val claim 128 , Arg-Arg claim 128 , Val-D-Cit claim 128 , Val-D-Lys claim 128 , Val-D-Arg claim 128 , D-Val-Cit claim 128 , D-Val-Lys claim 128 , D-Val-Arg claim 128 , D-Val-D-Cit claim 128 , D-Val-D-Lys claim 128 , D-Val-D-Arg claim 128 , D-Arg-D-Arg claim 128 , Ala-Ala claim 128 , Ala-D-Ala claim 128 , D-Ala-Ala claim 128 , D-Ala-D-Ala claim 128 , Ala-Met claim 128 , and Met-Ala.130. The compound of claim 125 , wherein:{'sub': 1', '2', '3', '4', '1', '2', '3', '4, 'R, R, R, R, R′, R′, R′ and R′ are all —H;'}{'sub': '6', 'Ris —OMe;'}X′ and Y′ are both —H;A and A′ are —O—; and{'sup': +', '+, 'M is H, Na or K.'}135. The conjugate of claim 132 , wherein P is a peptide containing 2 to 5 amino acid residues.136. The conjugate of claim 135 , wherein P is selected from Gly- ...

Saposin-a derived peptides and uses thereof

Disclosed herein are polypeptides and fusion polypeptides that have anti-angiogenic activity that can be used to inhibit tumor growth and tumor metastasis. The polypeptide consists of 9 or less consecutive amino acid residues (e.g., 8, 7, 6, 5, or 4) comprising the active core amino acid sequence DWLP, or an amino acid substitution variant thereof. Specific amino acid substitutions are disclosed herein. In some embodiments, the peptide consists essentially of 4-6 mers identified as exhibiting the activity of prosaposin A. Also disclosed herein are therapeutic compositions comprising the polypeptides and fusion polypeptides, and their use in the treatment, prevention, and inhibition of angiogenesis-related diseases and disorders such as cancer and cancer metastasis.

CROSSLINKED HYDROGEL COMPOSITIONS FOR REGULATING STATES OF ENCAPSULATED CANCER CELLS

The present invention discloses crosslinked poly(alkylene glycol) (PAG)-based hydrogel compositions, systems containing a plurality of cancer cells in contact with a cell culture media and encapsulated in the crosslinked PAG-based hydrogel composition and methods of making such crosslinked hydrogel compositions and systems. Also disclosed herein are methods of using such compositions and systems, such as, for example for screening an agent for effectiveness of the agent against cancer cells. Also disclosed herein are kits containing one or more components including one or more systems of the present disclosure and one or more instructions. 1. A method of regulating a state of cancer cells , the method comprising: a) a crosslinked poly(alkylene glycol) (PAG)-based hydrogel composition,', 'b) a cell culture media in contact with the crosslinked PAG-based hydrogel composition, and', 'c) a plurality of cancer cells in contact with the cell culture media and encapsulated in the crosslinked PAG-based hydrogel composition;, 'i) providing a system comprisingii) adding a reactant to the system, wherein the reactant is selected from the group consisting of a co-monomer, a cell-adhesive macromer, a hydrogel digesting agent and combinations thereof; and 'wherein each of the first and the second cancer state is selected from the group consisting of invasive growth, single cell restricted survival dormancy, single cell balanced survival dormancy and tumor mass balanced survival dormancy, such that the first state is different from the second state.', 'ii) adjusting a concentration of the reactant in the system, whereby the state of the cancer cells is either maintained in a first cancer state or switched from the first cancer state to a second state,'}2. The method according to claim 1 , wherein the step of providing a system further comprises forming the crosslinked PAG-based hydrogel composition by photopolymerizing a polymer-peptide macromer in the presence of a Type 1 ...

PEPTIDE ANALOGS OF ALPHA-MELANOCYTE STIMULATING HORMONE

Provided herein are stable peptide analogs of the native alpha-melanocyte stimulating hormone (α-MSH) having selectivity for the melanocortin 1 receptor (MC1R). Also provided herein are pharmaceutical preparations of the α-MSH peptide analogs, as well as methods of using these analogs in the treatment of medical and veterinary conditions involving MC1R. 1. A substantially pure compound that selectively binds melanocortin 1 receptor (MC1R) , said compound comprising a polypeptide having the sequence:{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'XaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaa,'}{'sub': '1', 'claim-text': [{'sub': '2', 'Xaais D-Pro, D-Ala or D-Lys;'}, {'sub': '3', 'Xaais D-Lys, D-Orn, D-Nle, D-Ala or D-Lys;'}, {'sub': '4', 'Xaais Gly, or D-Ala;'}, {'sub': '5', 'Xaais D-Trp, Trp, D-3-benzothienyl-Ala, D-5-hydroxy-Trp, D-5-methoxy-Trp, D-Phe, or D-Ala;'}, {'sub': '6', 'Xaais D-Arg, D-His, or D-Ala;'}, {'sub': '7', 'Xaais D-Cha, D-Phe, Phe, D-4-fluoro-Phg, D-3-pyridyl-Ala, D-Thi, D-Trp, D-4-nitro-Phe, or D-Ala;'}, {'sub': '8', 'Xaais D-His, His, D-Arg, Phe, or D-Ala;'}, {'sub': '9', 'Xaais D-Glu, D-Asp, D-citrulline, D-Ser, or D-Ala;'}, {'sub': '10', 'Xaais D-Met, D-buthionine, D-Ile, or D-Ala;'}, {'sub': '11', 'Xaais D-Ser, D-Ile or D-Ala;'}, {'sub': '12', 'Xaais D-Tyr, D-Ser, or D-Ala; and'}, {'sub': '13', 'Xaais D-Ser or D-Ala;'}], 'wherein Xaais D-Val, D-Ala or D-Lys;'}{'sub': 1-13', '1-3', '1-13, 'wherein no more than one Xaais D-Ala except when Xaaare all D-Ala, and no more than one Xaais an L-amino acid;'}or a pharmaceutically acceptable salt thereof.2. The compound of claim 1 , said compound comprising a polypeptide having the sequence:{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'XaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaa,'}{'sub': '1', 'claim-text': [{'sub': '2', 'Xaais D-Pro;'}, {'sub': '3', 'Xaais D-Lys, D-Orn or D-Nle;'}, {'sub': '4', 'Xaais Gly;'}, {'sub': '5', 'Xaais D-Trp, Trp, D-3- ...

METHODS AND COMPOSITIONS FOR DETECTING OR MEASURING CASPASES OR APOPTOSIS

Provided herein are compounds, enzyme substrates, compositions, kits, uses, and methods for detecting the presence or absence of a caspase enzyme, measuring the activity of a caspase enzyme, or detecting the presence or absence of apoptosis. The detection or measurement can occur through intracellular cleavage of a compound or enzyme substrate, which can lead to an increase in fluorescence, e.g., in the violet or red channel, through liberation of a nucleic acid binding dye from a peptide, such as liberation of a DNA-binding dye from a negatively charged peptide comprising a sequence recognized and cleaved by a caspase 2. The method according to claim 1 , wherein:{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'a) each R, R, R, R, R, R, R, R, R, R, R, Rand Ris independently H, halogen, or alkyl;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'b) each R, R, R, R, R, R, R, R, R, R, R, Rand Ris independently H, alkyl, or substituted alkyl;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'c) each R, R, R, R, R, R, R, R, R, R, R, Rand Ris independently H or alkyl;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'd) at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve of R, R, R, R, R, R, R, R, R, R, R, Rand Rare H; or'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13, 'e) each R, R, R, R, R, R, R, R, R, R, R, Rand Ris H.'}3. The method according to any one of - claim 1 , wherein:a) X is —N(R)— wherein R is H, halogen, alkyl, or substituted alkyl;b) X is —N(R)— wherein R is alkyl or substituted alkyl;c) X is —N(R)— wherein R is alkyl;d) X is —N(R)— wherein R is methyl, ethyl, propyl, or isopropyl;e) X is —N(R)— wherein R is methyl or ethyl; or{'sub': '3', 'f) X is —N(CH)—.'}4. The method according to any one of - claim 1 , wherein:a) Y is alkyl;b) Y is methyl, ethyl, propyl, or isopropyl;c) Y is methyl or ...

COMPOSITION FOR IMPROVING MEMORY, LEARNING ABILITY, AND COGNITIVE ABILITY

There is provided a composition for improving memory, learning ability, and cognitive ability. It has been confirmed that a peptide having a C-terminal region ended to GAG had an effect of improving the memory. In order for the peptide to have the effect, it has been confirmed that the peptide should be a peptide of which the length consists of at least 4 amino acids. Further, it has been confirmed that a peptide of which the length of the peptide having the C-terminal region ended to GAG consists of 5 to 9 amino acids has the same effect. As a result, the peptide of the present invention can be used as the composition for improving memory, learning ability, and cognitive ability. 1. A peptide comprising an amino acid sequence , wherein the amino acid sequence of the peptide is selected from the group consisting of SEQ ID NO:7(QAGAG) , SEQ ID NO:8(SGGAG) , and SEQ ID NO:9(GAGGAGGAG).2. The peptide of claim 1 , wherein the peptide is artificially synthesized.3. A pharmaceutical composition for preventing or treating a memory claim 1 , cognitive claim 1 , or learning disorder claim 1 , including the peptide of as an active ingredient.4fasciola hepatica. The pharmaceutical composition of claim 3 , wherein the memory claim 3 , cognitive claim 3 , or learning disorder is a memory claim 3 , cognitive claim 3 , or learning disorder caused by aging claim 3 , Alzheimer's disease claim 3 , schizophrenia claim 3 , Parkinson's disease claim 3 , Huntington's disease claim 3 , pick disease claim 3 , Creutzfeldt-Jakob disease claim 3 , depression claim 3 , aging claim 3 , head injury claim 3 , stroke claim 3 , CNS hypoxia claim 3 , cerebral ischemia claim 3 , encephalitis claim 3 , forgetfulness claim 3 , traumatic brain injury claim 3 , hypoglycaemia claim 3 , Wernicke-Korsakoff syndrome claim 3 , drug addiction claim 3 , epilepsy claim 3 , claim 3 , hippocampal sclerosis claim 3 , headache claim 3 , brain aging claim 3 , dementia claim 3 , frontotemporal lobar degeneration claim ...

COMPOSITION FOR IMPROVING MEMORY, LEARNING ABILITY, AND COGNITIVE ABILITY

There is provided a composition for improving memory, learning ability, and cognitive ability. It has been confirmed that a peptide having a C-terminal region ended to GAG had an effect of improving the memory. In order for the peptide to have the effect, it has been confirmed that the peptide should be a peptide of which the length consists of at least 4 amino acids. Further, it has been confirmed that a peptide of which the length of the peptide having the C-terminal region ended to GAG consists of 5 to 9 amino acids has the same effect. As a result, the peptide of the present invention can be used as the composition for improving memory, learning ability, and cognitive ability. 1. A polynucleotide encoding the peptide comprising an amino acid sequence , wherein the amino acid sequence of the peptide is selected from the group consisting of SEQ ID NO:7(QAGAG) , SEQ ID NO:8(SGGAG) , and SEQ ID NO:9(GAGGAGGAG).2. The polynucleotide of claim 1 , wherein the polynucleotide is useful for preventing or treating a memory claim 1 , cognitive claim 1 , or learning disorder.3fasciola hepatica. The polynucleotide of claim 1 , wherein the memory claim 1 , cognitive claim 1 , or learning disorder is a memory claim 1 , cognitive claim 1 , or learning disorder caused by aging claim 1 , Alzheimer's disease claim 1 , schizophrenia claim 1 , Parkinson's disease claim 1 , Huntington's disease claim 1 , pick disease claim 1 , Creutzfeldt-Jakob disease claim 1 , depression claim 1 , aging claim 1 , head injury claim 1 , stroke claim 1 , CNS hypoxia claim 1 , cerebral ischemia claim 1 , encephalitis claim 1 , forgetfulness claim 1 , traumatic brain injury claim 1 , hypoglycaemia claim 1 , Wernicke-Korsakoff syndrome claim 1 , drug addiction claim 1 , epilepsy claim 1 , claim 1 , hippocampal sclerosis claim 1 , headache claim 1 , brain aging claim 1 , dementia claim 1 , frontotemporal lobar degeneration claim 1 , tumor claim 1 , normal pressure hydrocephalus claim 1 , HIV claim 1 , ...

INHIBITORS

The present invention relates to compounds having the formula [Co-enzyme A or analogue thereof]-Z1-Z2-Z3-Z4, wherein Z1 is a linker, Z2 and Z3 are peptides or peptide-based moieties, and Z4 is a C-terminal group. The invention also provides pharmaceutical compositions comprising compounds of the invention, and their uses for the treatment of cancer, wound healing and nerve regeneration, inter alia. 1. A compound of formula Co-enzyme A-acetyl-SS(Nle)P-NH(SEQ ID NO: 4).4. The compound as claimed in claim 2 , wherein Z1 is acetyl.10. The compound as claimed in claim 2 , wherein Z3 is K or is absent.11. The compound as claimed in claim 2 , wherein Z4 is —NHor N-alkyl.12. The compound as claimed in claim 2 , which additionally comprises a targeting moiety.13. The compound as claimed in claim 12 , wherein the targeting moiety is a cancer cell-targeting moiety.14. The peptidomimetic of a compound as claimed in .15. A pharmaceutical composition comprising a compound as claimed in claim 2 , optionally together with one or more diluents claim 2 , carriers or excipients.16. (canceled)17. A method of treating or preventing a disease or disorder associated with NatA activity claim 2 , the method comprising administering an effective amount of a compound as claimed in claim 2 , wherein Z2 has the sequence of SEQ ID NO: 1 claim 2 , to a subject in need thereof.1819-. (canceled)20. A method of treating or preventing cancer claim 2 , the method comprising administering an effective amount of a compound as claimed in claim 2 , wherein Z2 has the sequence of SEQ ID NO: 1 claim 2 , to a subject in need thereof.2122-. (canceled)23. The 4-method as claimed in claim 20 , wherein the cancer is selected from the group consisting oflymphomas, leukaemias, neuroblastomas, glioblastomas, carcinomas, adenocarcinomas, melanomas, lung cancer, breast cancer, hepatocellular carcinoma, colorectal cancer, pancreatic cancer, ovarian cancer, gastric cancer, non-small cell lung cancer, papillary thyroid ...

SHORT BIO-ACTIVE PEPTIDES FOR PROMOTING WOUND HEALING

Peptides having four to six amino acid residues are disclosed that possess biological activity. These peptides constitute short fragments of the peptide HB-107 (MPKEKVFLKIEKMGRNIRN), which itself is a fragment of the antimicrobial protein cecropin B, and exhibit cell stimulatory and migratory properties. The inventive peptides comprise four to six contiguous amino acid residues located between position 11 and 16 of HB107 (MPKEKVFLKIEKMGRNIRN), namely EKMGRN. The disclosed peptides comprise a useful agent for the medical treatment of injury to the skin, such as from diabetic ulcers. The peptides also are effective in preventing and reversing skin surface damage resulting from various environmental insults Importantly, the therapeutic effects of the peptides manifest at concentrations equal to or greater than those of peptide HB-107, and thus represent a less expensive, more versatile means for developing effective therapies. Methods for the production and use of these peptides are also disclosed. 1. An isolated peptide , wherein the sequence of the peptide consists SEQ ID NO:4 (EKMG) , SEQ ID NO: 5 (MGRN) or SEQ ID NO: 2 (KMGRN) , wherein the peptide is in free acid form , amidated at the carboxy terminus or lipidated at the amine terminus.2. The peptide of which is SEQ ID NO:4 (EKMG) or SEQ ID NO:5 (MGRN) or SEQ ID NO 2 (KMGRN).3. The peptide of which comprises either or both L- and D-amino acid enantiomers.4. A composition comprising at least one peptide according to and a pharmaceutically acceptable carrier.5. The composition of claim 4 , wherein the peptide is present in a concentration ranging from about 0.1 μg/mL to about 500 μg/mL claim 4 , or about 0.1 μg/mL to about 20 mg/mL.6. The composition of claim 4 , wherein the composition is in the form of an aerosol claim 4 , emulsion claim 4 , liquid claim 4 , lotion claim 4 , solution claim 4 , gel claim 4 , micro-encapsulation claim 4 , cream claim 4 , paste claim 4 , ointment claim 4 , powder or foam or is ...

NOVEL AGENTS TARGETING INHIBITOR OF APOPTOSIS PROTEINS

Disclosed herein, inter alia, are methods of use and composition of novel inhibitors that target the Smac binding site of a variety of inhibitor of apoptosis proteins that contain a Bir domain, including XIAP, cIAP1, cIAP2, or other IAP proteins. 2. The compound claim 1 , or a pharmaceutical salt thereof claim 1 , or a prodrug thereof claim 1 , of claim 1 , wherein Ris unsubstituted alkyl claim 1 , unsubstituted heteroalkyl claim 1 , unsubstituted cycloalkyl claim 1 , unsubstituted heterocycloalkyl claim 1 , unsubstituted aryl claim 1 , or unsubstituted heteroaryl.3. The compound claim 1 , or a pharmaceutical salt thereof claim 1 , or a prodrug thereof claim 1 , of claim 1 , wherein Ris —CH claim 1 , —CH claim 1 , —CF claim 1 , —CHF claim 1 , —CHF claim 1 , —CHCF claim 1 , —CFCH claim 1 , —CHOH claim 1 , —CFOH claim 1 , or —CHFOH.4. The compound claim 1 , or a pharmaceutical salt thereof claim 1 , or a prodrug thereof claim 1 , of claim 1 , wherein Lis a bond claim 1 , —NH— claim 1 , —O— claim 1 , —S— claim 1 , —C(O)— claim 1 , —C(O)NH— claim 1 , —NHC(O)— claim 1 , —NHC(O)NH— claim 1 , —C(O)O— claim 1 , —OC(O)— claim 1 , —(CH)— claim 1 , —(CH)O— claim 1 , —(CH)NHC(O)— claim 1 , —(CH)S— claim 1 , —(CH)C(O)NH— claim 1 , —O(CH)— claim 1 , —(CH)NH— claim 1 , —(CH)NHCH— claim 1 , or —(CH)C(O)—.56-. (canceled)89-. (canceled)11. (canceled)13. The compound claim 1 , or a pharmaceutical salt thereof claim 1 , or a prodrug thereof claim 1 , of claim 1 , wherein Ris independently halogen claim 1 , —CX claim 1 , —CHX claim 1 , —CHX claim 1 , —OH claim 1 , —OCX claim 1 , —OCHX claim 1 , —OCHX claim 1 , unsubstituted C-Calkyl claim 1 , or unsubstituted 2 to 3 membered heteroalkyl.14. (canceled)15. The compound claim 1 , or a pharmaceutical salt thereof claim 1 , or a prodrug thereof claim 1 , of claim 1 , wherein each Rand Ris independently hydrogen claim 1 , —F claim 1 , —OH claim 1 , —OCF claim 1 , —OCH claim 1 , —OCHCH claim 1 , or —NHC(NH)NH.16. (canceled)17. The compound ...

CYTOTOXIC BENZODIAZEPINE DERIVATIVES

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VI). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. 177-. (canceled)79. The conjugate of claim 78 , wherein the heavy chain CDR2 comprises SEQ ID NO:7.80. The conjugate of claim 78 , wherein the anti-folate receptor antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO:11; and a light chain variable region having the amino acid sequence of SEQ ID NO:12 or SEQ ID NO:1381. The conjugate of claim 78 , wherein the anti-folate receptor antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:8; and a light chain having the amino acid sequence of SEQ ID NO:9 or SEQ ID NO:10.82. The conjugate of claim 81 , wherein the anti-folate receptor antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:8; and a light chain having the amino acid sequence of SEQ ID NO:10.83. The conjugate of claim 78 , wherein the anti-folate receptor antibody is huMOV19 antibody.84. A pharmaceutical composition comprising the conjugate of and a pharmaceutically acceptable carrier.85. A method of treating a cancer in a mammal claim 78 , comprising administering to said mammal a therapeutically effective amount of the conjugate of claim 78 , and optionally claim 78 , a chemotherapeutic agent.86. The method of claim 85 , wherein the cancer is ovarian cancer claim 85 , pancreatic cancer claim 85 , cervical cancer claim 85 , melanoma claim 85 , lung cancer claim 85 , breast cancer claim 85 , squamous cell carcinoma of the head and neck claim 85 , prostate cancer claim 85 , endometrial cancer claim 85 , lymphoma ...

Methods for inhibiting tumor cell proliferation

The present invention provides methods, compounds, and pharmaceutical compositions for inhibiting tumor cell proliferation, by administering an effective amount of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II (AII), AII analogues, AII fragments or analogues thereof or AII AT2 type 2 receptor agonists to a subject.

Modified peptides as potent inhibitors of the psd-95/nmda receptor interaction

The present invention is directed to the provision of small molecule inhibitors of the PSD-95/NMDA receptor interaction, employing an undecapeptide corresponding to the C-terminal of the NMDA as a template for finding lead candidates. A compound (NMDAR/PSD-95 inhibitor) of the invention includes a peptide or peptide analogue comprising at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof, and X is selected from among A, Q, D, N, N -Me-A, N-Me-Q, N -Me-D, and N -Me-N or an analogue thereof, wherein an amino-terminal residue of the peptide is N -alkylated. Alternatively the compound of the invention comprises a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, where the first and second peptide or peptide analogue each comprise at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof, and X is selected from among A, Q, D, N, N-Me-A, N -Me-Q, N-Me-D, and N -Me-N or an analogue thereof.

Aromatic compound containing specific branch

The present invention provides a particular branched chain-containing aromatic compound. The branched chain-containing aromatic compound of the present invention is easily-soluble in isopropyl acetate superior in liquid-separation operability, and can be used for a production method of peptide and the like, which provides a final product simply by extraction separation, without crystallization and isolation of each intermediate in each step.

Immunoreactive compounds

Peptide conjugates and fluorescence detection methods for intracellular caspase assay

Polypeptides labelled with a donor and acceptor pair of dyes selected from a dibenzorhodamine dye and a diamino-benzophenoxazine dye are peptide conjugates which are useful for intracellular and bead-based assays with fluorescence detection. Peptide conjugates with a caspase-recognition site undergo cleavage into peptide fragments which may be detected, located, and quantitated by the changes in fluorescence. Intracellular cleavage of peptide conjugates is correlated with apoptosis.

Process for producing polypeptides

Laccase mutants

By analyzing the three-dimensional structure of the Coprinus laccase structural parts or specific amino acid residues can be identified, which from structural or functional considerations appear to be important for the oxidative stability of a laccase. When comparing the three-dimensional structure of the Coprinus laccase structure with known amino acid sequences of various laccases, it has been found that several similarities exist between the sequences.

Patent DE3100974C2

Synthetic peptide surfactant with covalently bound antioxidants

황산화제 부분을 갖는 3 내지 4 아미노산 잔기의 폴리펩티드, 및 천연 폐계면활성제와 회합된 하나 이상의 지질로 이루어지는 지질과의 복합체로 이루어지는, 항산화적 특성을 갖는 합성 폐 계면활성제를 제조하였다. 이들 계면활성제는 호흡 곤란 증후군의 치료에 유용하다. A synthetic pulmonary surfactant having antioxidant properties comprising a complex of a polypeptide of 3 to 4 amino acid residues having a sulfating agent moiety and lipids consisting of at least one lipid associated with a natural pulmonary surfactant was prepared. These surfactants are useful in the treatment of respiratory distress syndrome.

Diamine-linked receptor-specific cyclic peptide

하기 화학식 I의 수용체-특이적 고리형 펩티드, 하기 화학식의 펩티드를 포함하는 조성물 및 제형, 및 화학식 I의 멜라노코르틴 수용체-특이적 고리형 펩티드를 사용하여 멜라노코르틴 수용체-매개된 질환, 적응증, 병태 및 증후군을 예방, 개선 또는 치료하는 방법이 개시된다: [화학식 I] (상기 식에서, Xaa 1 , Xaa 2 , Xaa 3 , x, R1, R2, R3 및 R4는 명세서에 정의된 바와 같음).

PEPTIDES AND POLYPEPTIDES FROM THE RAT SUB-MAXILLARY GLAND, CORRESPONDING MONOCLONAL AND POLYCLONAL ANTIBODIES, HYBRIDOMAS AND APPLICATIONS THEREOF FOR DIAGNOSIS, DETECTION OR THERAPEUTIC PURPOSES

Peptide and method for its preparation

FIELD: medicine; methods for producing biologically active substances with immunoregulatory action; may be used in medicine, veterinary practice and experimental biochemistry. SUBSTANCE: proposed is novel, synthetic, biologically active peptide with immunoregulatory action and having the formula: X-Glu-Trp-Y, where X is H or Gly, Ala, Leu, Ile, Val, NVal, Pro, Tyr, Phe, Trp, D-Ala, D-Leu, D-Ile, D-Val, D-NVal, D-Pro, D-Tyr, D-Phe, D-Trp, aminobutyric acid, aminocapric acid; Y is Gly, Ala, Leu, Ile, Val, NVal, Pro, Tyr, Phe, Trp, D-Ala, D-Leu, D-Ile, D-Val, D-NVal, D-Pro, D-Tyr, D-Phe, D-Trp, aminobutyric acid, aminocapric acid, OH, mono- or disubstituted (C 1 -C 3 ). amide. Peptide is synthesized in solution by progressively growing molecular chain from C-terminal and maximum blocking functional groups. Synthesis makes departure from amino acid alkyl ether and uses activated ethers, mixed anhydrides and tert.butylhydroxycarbonyl amino acids. EFFECT: higher efficiency. 2 cl, 2 tbl гэ ос ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (51) МПК ВИ” 2107 691 ' 13) СЛ С 07 К 5/065, А 61 К 38/08 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 95102461/04, 02.03.1995 (46) Дата публикации: 27.03.1998 (56) Ссылки: 1. ЗЦ, авторское свидетельство 1737138, кл. А 61 К 38,00, 1995. 2. СН, патент 659586, кл. С 07 К 5/08, 1986. 3. РСТ, патент \!О 089/06134, кл. А 61 К 37/02, 1989. 4. ЕР, заявка 0230052, кл. С ОТК 1100, 1987. 5. ЕР, заявка 0406931, кл. С 07 К 5/02, 1991. 6. 4$, патент 5021551, кл. А 61 К 37/02, 1991. 7. Ц$, патент 5013723, кл. А 61 К 37/02, 1991. (71) Заявитель: Инженерный центр пептидных препаратов "Пептос" (72) Изобретатель: Дейгин В.И., Коротков А.М. (73) Патентообладатель: Дейгин Владислав Исакович, Коротков Андрей Марксович (54) ПЕПТИД И СПОСОБ ЕГО ПОЛУЧЕНИЯ (57) Реферат: Изобретение относится к медицине, а именно к способам получения биологически активных веществ, обладающих иммуннорегулирующими свойствами, и может ...

Polyaminoacids as builders for detergent formulations

Polyaminoacides are used as builders or co-builders in the formualtion of detergents. These polyaminoacids which are highly efficient as complexing agents, have good heat resistance and pH stability and are entirely biodegradable, are represented by the general formula: the substituents being defined in the description. The detergent formulations contain, apart from the above builders, surface active agents, alumina-silicates and additives chosen from neutral salts, enzymes, bleaching agents, stabilizers, anti-foaming agents, perfumes, and bactericides.

Polyaminoacids as builders for formulations of detergents

Polyaminoacid builders or co-builders having the general formula: ##STR1## that are useful in the formulations of detergents are disclosed. Preferred detergent formulations contain from 5 to 50 percent by weight of the polyaminoacid builder, preferably polyaspartic aicd or polyglutamic acid, together with surface-active agents, aluminosilicates and other detergent additives.

Polyaminoacids as builders for detergent formulations

Materials and methods relating to cardiovascular imaging

The invention provides conjugates for imaging plaques, such as cardiovascular plaques, as well as associated pharmaceutical compositions. Other aspects of the invention include methods for administering and imaging such conjugates and compositions, and using the imaging to characterise plaques. The conjugates of the invention distinguish between tropoelastin and elastin in plaques. The presence of tropoelastin can act as an indication that a plaque is liable to rupture or erode. Such information allows assessment of disease progression and response to treatment.

Regulation of autophagy pathway phosphorylation and uses thereof

The invention relates to polypeptides and proteins known to function in the autophagy pathway that have novel phosphorylation sites. The invention also relates to antibodies specific to these polypeptides and proteins that are phosphorylated or not phosphorylated at novel phosphorylated sites. The invention also relates to methods of producing these antibodies and use of these antibodies in the treatment of diseases related to autophagocytosis.

Peptide pulmonary surfactants and therapeutic mixtures

본 발명은 알파 나선형 구조를 갖는 3 내지 4개 아미노산 잔기의 폴리펩티드 및 공유 결합된 장쇄 아실기의 복합체로 이루어지는 합성 폐 계면활성제에 관한 것이다. 펩티드는 회합된 1종 이상의 지질과의 복합체로 이루어지는 경우 호흡곤란증에 연관된 증세에 유용하다. The present invention relates to a synthetic pulmonary surfactant comprising a complex of a polypeptide of 3 to 4 amino acid residues having an alpha helical structure and a covalently bonded long chain acyl group. Peptides are useful in the symptoms associated with respiratory distress if they are composed of complexes with one or more associated lipids.

Peptides and methods using same for diagnosing and treating amyloid-associated diseases

A peptide comprising at least 5 amino acid residues and less than 15 amino acid residues, the peptide including an amino acid sequence as set forth in SEQ ID NO: 7 as well as pharmaceutical compositions, kits and methods for diagnosing and treating amyloid associated diseases.

Peptide binding the KLVFF-sequence of amyloid-β

The invention relates to compounds of formula (I) or (II), which are of interest especially for inhibition of polymerization of amyloid β peptide, as model substances for synthesis of amyloid β peptide-ligands, as tools for the identification of other organic compounds with similar functional properties and/or as ligands for detection of amyloid deposits using e.g., positron emission tomography (PET). Formula (II) is: R 1 -A′-Y′-Leu-X′-Z′-B′-R 2 in which X′ means any group or amino acid imparting to the compound according to formula (I) the ability to bind to the KLVFF-sequence in amyloid β peptide, or two amino acids imparting the same ability, but with the proviso that one is not proline; Y′ means any amino acid; Z′ means any non-acidic amino acid; A′ means a direct bond or an α-amino acid bonded at the carboxyl terminal of the α-carboxy group or a di-, tri-, tetra- or pentapeptide bonded at the carboxyl terminal of the α-carboxy group; B′ means a direct bond or an α-amino acid bonded at the α-nitrogen or a di-, tri, tetra- or pentapeptide bonded at the α-nitrogen of the N-terminal α-amino acid; R 1 is H or —CO—R 3 bonded at the α-amino group of A′; R 2 is H, —OR 4 or NR 5 R 6 , all bonded to the α-carboxyl group of the α-carboxyterminal of B′; R 3 and R 4 are straight or branched carbon chain of 1-4 carbon atoms; R 5 and R 6 are independently H, alkyl, cycloalyl, aryl or substituted aryl or together are —(CH 2 ) n — where n is 4-5; and R 1 and R 2 together can form a hydrocarbon ring or heterocyclic ring; all α-amino acids being either D- or L-isomers.

N-Carboxyalkyl-auristatins and their use

Compuesto de fórmula (I)**Fórmula** en la que L representa alcanodiilo (C1-C12) de cadena lineal, que puede estar sustituido hasta cuatro veces con metilo y en el que (a) dos átomos de carbono pueden estar unidos en puente en una relación 1,2, 1,3 ó 1,4 entre sí incluyendo los átomos de carbono que se encuentran dado el caso entre los mismos formando un anillo de cicloalquilo (C3-C6) o un anillo de fenilo o (b) hasta tres grupos CH2 no adyacentes entre sí pueden estar intercambiados por -O-, R1 representa hidrógeno o metilo, R2 representa isopropilo, isobutilo, sec-butilo, terc-butilo, 1-hidroxietilo, fenilo, bencilo, 4-hidroxibencilo, 1-feniletilo, difenilmetilo, 1H-imidazol-4-ilmetilo o 1H-indol-3-ilmetilo, o R1 y R2 junto con el átomo de carbono, al que están ambos unidos, forman un grupo 2-fenilciclopropano- 1,1-diilo de fórmula**Fórmula** , en la que indica los puntos de unión con las partes restantes de la molécula, y T representa un grupo de fórmula -C(>=O)-OR3, -C(>=O)-NR4R5, -C(>=O)-NH-NH-R6 o -CH2-O-R7, en las que R3 significa hidrógeno, alquilo (C1-C6) o cicloalquilo (C3-C10), pudiendo el alquilo (C1-C6) estar sustituido con fenilo, naftilo o cicloalquilo (C3-C10), R4 significa hidrógeno o alquilo (C1-C6), R5 significa hidrógeno, alquilo (C1-C6) o cicloalquilo (C3-C10), pudiendo el alquilo (C1-C6) estar sustituido con fenilo, o R4 y R5 están unidos entre sí y junto con el átomo de nitrógeno, al que están unidos, forman un aza-heterociclo saturado, de 5 a 7 miembros, que puede contener un heteroátomo de anillo adicional de la serie >N-H, >N-CH3 o -O-, que se encuentra en una posición 1,3 o dado el caso 1,4 en relación con el átomo de nitrógeno mencionado en primer lugar, R6 significa alquilo (C1-C6), alquilcarbonilo (C1-C6), fenilo o benzoílo, y R7 significa alquilo (C1-C6), que puede estar sustituido con fenilo, pudiendo el fenilo estar a su vez sustituido con alcoxicarbonilo (C1-C6) o carboxilo, así como sus sales, solvatos y solvatos de ...

A kind of active polypeptide QEIP of inhibition Angiotensin-Converting and its application

本发明提供了一种抑制血管紧张素转换酶活性的多肽及其应用，属于生物技术领域。本发明所述多肽的氨基酸序列如SEQ ID NO.1所示(Gln‑Glu‑Ile‑Pro)，针对ACE靶标均具有抑制活性，从而表现出同时具有降血压的特性；且多肽的活性与浓度存在量效关系，属于新的具ACE抑制活性功能肽，可将其用于制备ACE抑制剂或降压药物。

Methods and compositions for detecting or measuring caspases or apoptosis

Provided herein are compounds, enzyme substrates, compositions, kits, uses, and methods for detecting the presence or absence of a caspase enzyme, measuring the activity of a caspase enzyme, or detecting the presence or absence of apoptosis. The detection or measurement can occur through intracellular cleavage of a compound or enzyme substrate, which can lead to an increase in fluorescence, e.g., in the violet or red channel, through liberation of a nucleic acid binding dye from a peptide, such as liberation of a DNA-binding dye from a negatively charged peptide comprising a sequence recognized and cleaved by a caspase.

Catalytically active recombinant memapsin and methods of use thereof

Methods for the production of purified, catalytically active, recombinant memapsin (2) have been developed. The substrate and subsite specificity of t he catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin (2) substrate that can inhibit the function of memapsin (2). The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin (2). The substrate analogs contain a t least one analog of an amide bond which is not capable of being cleaved by memapsin (2). Processes for the synthesis of two substrate analogues includi ng isosteres at the sites of the critical amino acid residues were developed an d the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is bas ed on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Le u- Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (Fig. 1). The inhibition constant of OM99-2 is 1.6 x 109 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, as well as the importance of the various residues in binding. This information can beused by those skilled in the art to design new inhibitors, using commercially available software programs and techniques familiar to those in organic chemistry and enzymology, to design new inhibitors to memapsin (2), useful in diagnostics and for the treatment and/or prevention of Alzheimer's disease.

New agents targeting apoptosis inhibitor proteins

본원은 특히 XIAP, cIAP1, cIAP2 또는 다른 IAP 단백질을 포함하는, Bir 도메인을 함유하는 다양한 아폽토시스 억제제 단백질들의 Smac 결합 부위를 표적화하는 신규 억제제의 사용 방법 및 조성물을 개시한다.

Epitope tag for affinity-based applications

The present invention relates to an epitope tag useful in affinity-based applications. The invention further includes fusion proteins, methods for preparing fusion proteins, nucleic acid molecules encoding these fusion proteins and recombinant host cells which contain these nucleic acid molecules. The invention also relates to nanobodies and other affinity ligands specifically recognizing said epitope tag, and uses thereof in affinity-based applications.

Epitope tag for affinity-based applications

The present invention relates to an epitope tag useful in affinity-based applications. The invention further includes fusion proteins, methods for preparing fusion proteins, nucleic acid molecules encoding these fusion proteins and recombinant host cells which contain these nucleic acid molecules. The invention also relates to nanobodies and other affinity ligands specifically recognizing said epitope tag, and uses thereof in affinity-based applications.

Epitope tag for affinity-based applications

Described is an epitope tag useful in affinity-based applications. The invention further includes fusion proteins, methods for preparing fusion proteins, nucleic acid molecules encoding these fusion proteins and recombinant host cells that contain these nucleic acid molecules. The invention also relates to nanobodies and other affinity ligands specifically recognizing the epitope tag, and uses thereof in affinity-based applications.

A process for extraction of peptides and its application in liquid phase peptide synthesis

The present invention relates to a process for extraction of a peptide from a reaction mixture resulting from a peptide coupling reaction, the reaction mixture containing the peptide and a polar aprotic solvent selected from the group consisting of Λ/,Λ/-dimethylformamide, A/,A/-dimethylacetamide and A/-methyl-2-pyrrolidone, whereby the process comprises a step a) and a step b):step a) comprises the addition of a component a1 ), a component a2) and a component a3), whereby component a1) is an organic solvent 1, the organic solvent 1 is selected from the group consisting of 2-methyltetrahydrofuran and toluene, component a2) is water, and component a3) is an organic solvent 2, the organic solvent 2 is selected from the group consisting of ethylacetate, isopropylacetate, acetonitrile, tetrahydrofuran and n-heptane to the reaction mixture, so that a biphasic system with an organic layer and an aqueous layer is obtained; step b) comprises the subsequent separation of the organic layer containing the peptide from the aqueous layer. The extraction step is preferably used in a process for preparation of a peptide in liquid phase.

Small molecule drug conjugates

Un agente terapéutico dirigido que comprende un compuesto de fórmula (I): B - L - D (I), en la que: B es un resto de unión de bajo peso molecular para la anhidrasa carbónica IX (CAIX), en el que dicho resto de unión comprende un grupo terminal de fórmula (T2): **(Ver fórmula)** D es un resto de fármaco; y L es un grupo ligador que experimenta escisión in vivo para liberar dicho resto de fármaco en una forma activa, en el que dicho ligador L comprende un anillo de 1,2,3-triazol, en el que dicho resto de fármaco y resto de ligador están unidos a las posiciones 1 y 4 del anillo de triazol y la posición 5 del anillo de triazol también está opcionalmente sustituida. A targeted therapeutic agent comprising a compound of formula (I): B-L-D (I), wherein: B is a low molecular weight linking moiety for carbonic anhydrase IX (CAIX), wherein said linking moiety comprises a terminal group of formula (T2): **(See formula)** D is a drug moiety; and L is a linker group that undergoes cleavage in vivo to release said drug moiety in an active form, wherein said linker L comprises a 1,2,3-triazole ring, wherein said drug moiety and linker are attached to the 1 and 4 positions of the triazole ring and the 5 position of the triazole ring is also optionally substituted.

Methods for inhibiting tumor cell proliferation

Methods for inhibiting tumor cell proliferation

Methods for inhibiting tumor cell proliferation

The present invention provides methods, compounds, and pharmaceutical compositions for inhibiting tumor cell proliferation, by administering an effective amount of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II (AII), AII analogues, AII fragments or analogues thereof or AII AT 2 type 2 receptor agonists to a subject.

Methods for inhibiting tumor cell proliferation

The present invention provides methods, compounds, and pharmaceutical compositions for inhibiting tumor cell proliferation, by administering an effective amount of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II (AII), AII analogues, AII fragments or analogues thereof or AII AT 2 type 2 receptor agonists to a subject.

Methods for inhibiting tumor cell proliferation

Methods for inhibiting smooth muscle cell proliferation

The present invention provides improved methods and pharmaceutical compositions for inhibiting smooth muscle cell proliferation, and for treating and preventing conditions associated with smooth muscle cell proliferation, by administering an effective amount of angiotensinogen, angiotensin I (AI), AI analogues, AI fragments and analogues thereof, angiotensin II (AII) analogues, AII fragments or analogues thereof or AII AT2 type 2 receptor agonists to the subject.

Aromatic compound containing side chain

本发明提供特定的含有支链的芳香族化合物。本发明的含有支链的芳香族化合物易溶于分液操作性良好的乙酸异丙酯，能够用于肽等的制造方法，其中，仅经过抽提分离即可引向最终产物，无需在各步骤对各中间体进行结晶分离。

Tetrapeptide Having Anti-Aging And Anti-Inflammatory Activities And Cosmetic Composition Containing The Same

본 발명은 하기 화학식 1과 화학식 2로 표시되는 테트라펩타이드 및 이를 유효성분으로 함유하는 피부 노화 방지 및 피부 주름 개선, 항염용 화장료 조성물에 관한 것이다. 본 발명에 따른 테트라펩타이드는 콜라겐 분해효소인 MMPs생성 억제로 인한 주름 개선효과와 더불어 염증 억제 효과를 나타냄으로써 주름 및 염증개선에 탁월한 효능을 갖는 화장료를 제공한다. 특히, 상기 주름개선 및 항염용의 테트라펩타이드는 스킨, 로션, 크림, 파운데이션, 에센스, 젤, 팩, 포클린징, 바디오일, 립스틱, 마스카라, 메이크업베이스 또는 비누형태 등의 다양한 기초 화장료 조성물에 첨가하여 사용할 수 있으며 피부자극이 없고 피부안정성도 우수한 특징을 갖는다. [화학식 1] R-R 1 -Gly-Leu-Phe [화학식 2] R-Gly-Leu-Phe-R 2 (상기 화학식 1 및 화학식 2에서, R은 수소 또는 탄소수 1~18의 아실기 중에서 선택되거나 또는 적어도 하나 이상의 이중결합을 포함하는 알케닐기이며, Leu 는 D-Leu 또는 L-Leu, Phe는 D-Phe 또는 L-Phe이 될 수 있다. 또한 화학식 1과 화학식 2 중의 R 1 및 R 2 로 표시되는 부분은 각각 아미노산, 특히 20개의 자연계 아미노산과 비자연계 아미노산인 페닐글리신(Phenylglycine)중에서 선택될 수 있으며 C-말단은 카복실산 또는 아마이드 형태가 될 수 있다.) The present invention relates to a tetrapeptide represented by the following formula (1) and (2) and to skin anti-aging and skin wrinkle improvement, containing the same as an active ingredient, anti-inflammatory cosmetic composition. The tetrapeptide according to the present invention provides a cosmetic having excellent efficacy in improving wrinkles and inflammation by showing an anti-inflammatory effect as well as an anti-wrinkle effect due to the inhibition of the production of collagen degrading enzyme MMPs. In particular, the tetrapeptides for wrinkle improvement and anti-inflammatory are added to various basic cosmetic compositions such as skins, lotions, creams, foundations, essences, gels, packs, forking, body oils, lipsticks, mascaras, makeup bases or soap forms. It can be used and has no skin irritation and excellent skin stability. [Chemical Formula 1] RR 1 -Gly-Leu-Phe (2) R-Gly-Leu-Phe-R 2 (In Formula 1 and Formula 2, R is an alkenyl group selected from hydrogen or an acyl group having 1 to 18 carbon atoms or at least one double bond, Leu is D-Leu or L-Leu, Phe is D- can be Phe or L-Phe. in addition may be selected from formula I and the phenylglycine (phenylglycine) portions are each amino acid, especially the 20 natural amino acids and non-associated amino acid ...

LIPID ASSEMBLIES AND USES THEREOF AND SOME pH AND ELECTROSTATIC MODULATING LIPIDS TO BE USED IN SAID ASSEMBLIES

The present disclosure concerns modified lipid compounds and their use in the formation of lipid assemblies. Specifically are disclosed lipid assemblies comprising (a) an amphoteric lipid comprising in covalent association with (i) one or more acyl chains; (ii) one or more weak base moiety; (iii) one or more weak acid moiety; the lipid assembly also comprising (b) one or more additional lipids, at least one of which being a zwitterionic lipid. In some embodiments, the amphoteric lipid is a compound comprising (a) a tri-functional moiety; (b) two non-phosphate lipid chains associated with two of the functional moieties of said tri-functional moiety; (c) optionally a spacer moiety associated with the third of the functional moieties of said tri-functional moiety; and (d) a polyalkylamine optionally comprising a short peptide with one to several carboxylic acid residues. Also disclosed are the uses of the lipid assembly, inter alia, for transfection or cancer treatment.

Lipid assemblies and uses thereof and some pH and electrostatic modulating lipids to be used in said assemblies

Provided are modified lipid compounds and their use in the formation of lipid assemblies. Also provided are lipid assemblies including (a) an amphoteric lipid including in covalent association with (i) one or more acyl chains; (ii) one or more weak base moiety; (iii) one or more weak acid moiety; the lipid assembly also including (b) one or more additional lipids, at least one of which being a zwitterionic lipid. In some embodiments, the amphoteric lipid is a compound including (a) a tri-functional moiety; (b) two non-phosphate lipid chains associated with two of the functional moieties of said tri-functional moiety; (c) optionally a spacer moiety associated with the third of the functional moieties of said tri-functional moiety; and (d) a polyalkylamine optionally including a short peptide with one to several carboxylic acid residues. Further provided are the uses of the lipid assembly, inter alia, for transfection or cancer treatment.

Modified peptides as potent inhibitors of the psd-95/nmda receptor interaction

The present invention is directed to the provision of small molecule inhibitors of the PSD-95/NMDA receptor interaction, employing an undecapeptide corresponding to the C-terminal of the NMDA as a template for finding lead candidates. A compound (NMDAR/PSD-95 inhibitor) of the invention includes a peptide or peptide analogue comprising at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof, and X is selected from among A, Q, D, N, N -Me-A, N-Me-Q, N -Me-D, and N -Me-N or an analogue thereof, wherein an amino-terminal residue of the peptide is N -alkylated. Alternatively the compound of the invention comprises a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, where the first and second peptide or peptide analogue each comprise at least four peptide bonded residues having the sequence YTXV or YSXV, wherein Y is selected from among E, Q, and A, or an analogue thereof, and X is selected from among A, Q, D, N, N-Me-A, N -Me-Q, N-Me-D, and N -Me-N or an analogue thereof.