Method of spatially controlling catalysis of a chemical reaction

The present invention provides a method of spatially controlling catalysis of a chemical reaction at a surface of a substrate. With this method, a substrate is provided with two or more independently addressable electrodes at or near the surface of the substrate. Next, a first potential is applied to one or more of the electrodes. This first potential is sufficient to electrochemically generate an active catalyst from an inactive catalyst proximal to any electrode(s) that are at this first potential. Simultaneously, a second potential is applied to all other electrodes. This second potential serves to deactivate any active catalyst that may diffuse from the proximity of the electrode(s) that are at the first potential. This method results in spatially selective activation of catalyst at the electrode(s) that are at the first potential, and hence spatial localization of a chemical reaction catalyzed by the active catalyst.

COMPOSITIONS AND METHODS FOR DELIVERING A SUBSTANCE TO A BIOLOGICAL TARGET

The present application provides compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reaction for rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target. 1. A composition for delivering an agent to a selected biological target , the composition comprising:a first component attached to a ligand that is specific for the biological target; anda second component attached to the agent;wherein the first and second components are each selected from either a diene or a dienophile and are reactants for the inverse electron demand Diels-Alder reaction.2. The composition of claim 1 , wherein the agent is selected from either a detectable agent or therapeutic agent.3. The composition of claim 2 , wherein the detectable agent is selected from the group consisting of organic small molecules claim 2 , inorganic compounds claim 2 , nanoparticles claim 2 , enzymes or enzyme substrates claim 2 , fluorescent materials claim 2 , luminescent materials claim 2 , bioluminescent materials claim 2 , radioactive materials claim 2 , and contrast agents.4. The composition of claim 2 , wherein the detectable agent is linked to a diene claim 2 , and undergoes fluorogenic activation in the presence of the strained dienophile.5. The composition of claim 2 , wherein the therapeutic agent is a small molecule claim 2 , enzyme inhibitor claim 2 , receptor protein inhibitor claim 2 , small interfering RNA (siRNA) claim 2 , cytotoxin claim 2 , radioactive ion claim 2 , or other therapeutic agent.6. A method of delivering a detectable agent to a biological target claim 2 , the method comprising:contacting a biological target with a ligand, wherein the ligand is linked to a first component selected from either a diene or a dienophile, to form a ligand-target conjugate;contacting the ligand-target conjugate with a second component that is selected from either a diene or a dienophile and participates in an inverse electron ...

IN SITU LIPID SYNTHESIS FOR PROTEIN RECONSTITUTION

Described herein, inter alia, are compositions and methods useful for the reconstitution of membrane proteins. 186-. (canceled)87. A method for forming a lipid membrane comprising a membrane protein , the method comprising:(i) adding a reactive surfactant comprising a reactive thioester moiety to a first solution which comprises the membrane protein; thereby forming a second solution which comprises the reactive surfactant and the membrane protein; and(ii) adding a phosphatidylcholine compound to the second solution, thereby forming a synthetic phospholipid; wherein the synthetic phospholipid forms a lipid membrane comprising the membrane protein.88. The method of claim 87 , comprising solubilizing the membrane protein in a first surfactant to form the first solution.89. The method of claim 88 , wherein the first surfactant is a nonionic alkyl glucoside.90. The method of claim 88 , wherein the first surfactant is n-dodecyl-β-D-maltoside.91. The method of claim 87 , wherein the reactive surfactant comprising a reactive thioester moiety is a maltoside surfactant.93. The method of claim 87 , wherein the phosphatidylcholine compound is a lysophosphatidylcholine compound.95. The method of claim 94 , wherein Ris an unsubstituted C-Calkyl or an unsubstituted C-Calkenyl.97. The method of claim 96 , wherein Ris an unsubstituted C-Calkyl or an unsubstituted C-Calkenyl.98. The method of claim 87 , wherein the membrane protein is a G protein-coupled receptor.99. The method of claim 87 , wherein the membrane protein is a 5-hydroxytryptamine receptor claim 87 , an acetylcholine receptor claim 87 , an adenosine receptor claim 87 , an angiotensin receptor claim 87 , an apelin receptor claim 87 , a bile acid receptor claim 87 , a bombesin receptor claim 87 , a bradykinin receptor claim 87 , a cannabinoid receptor claim 87 , a chemerin receptor claim 87 , a chemokine receptor claim 87 , a cholecystokinin receptor claim 87 , a Class A Orphan receptor claim 87 , a dopamine receptor ...

Amphiphilic thiol compounds and uses thereof

Provided herein are, inter alia, amphiphilic thiol compounds and methods of using the same for the purpose of depalmitoylating proteins in cellular membranes (e.g., plasma membranes). The compounds provided herein include an amphiphilic tail, which enables them to associate with a cellular membrane and depalmitoylate (cleave native S-palmitoyl groups from) a protein in said membrane by native chemical ligation thereby triggering the protein's release from the plasma membrane. The compounds (amphiphilic thiol compounds of formula (I), (II), (III)) are, inter alia, useful for the treatment of diseases caused or associated with aberrant depalmitoylation of certain proteins (e.g., HRas, EGFR).

FUNCTIONALIZED 1,2,4,5-TETRAZINE COMPOUNDS FOR USE IN BIOORTHOGONAL COUPLING REACTIONS

The present application relates to functionalized 1,2,4,5-tetrazine compounds. The compounds are useful in compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reactions for the rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target. 165-. (canceled)68. The peptide claim 66 , polypeptide or protein of claim 66 , wherein Ris hydrogen claim 66 , (C-C)alkyl claim 66 , or (C-C)haloalkyl.69. The peptide claim 68 , polypeptide or protein of claim 68 , wherein A is absent claim 68 , n2 is 0 and n1 is 1.71. The peptide claim 70 , polypeptide or protein of claim 70 , wherein n2 is 0.73. The peptide claim 72 , polypeptide or protein of claim 72 , wherein n1 is 3 claim 72 , 4 or 5 claim 72 , and n2 is 0 claim 72 , 1 claim 72 , or 2.75. The peptide claim 74 , polypeptide or protein of claim 74 , wherein n2 is other than 0 and n1 is 4.77. The peptide claim 76 , polypeptide or protein of claim 76 , wherein n1 is 1 or 2 and n2 is 5.79. The peptide claim 78 , polypeptide or protein of claim 78 , wherein n1 is 3 claim 78 , 4 or 5 and n2 is 0.81. The peptide claim 66 , polypeptide or protein of claim 66 , wherein the amino acid has (L) configuration.83. The method of claim 82 , wherein Ris hydrogen claim 82 , tert-butyloxycarbonyl or 9-fluorenylmethoxycarbonyl and Ris hydrogen or (C-C)alkyl.85. A peptide claim 82 , polypeptide or protein prepared by the process of . This application is a continuation of U.S. patent application Ser. No. 14/437,905, filed Apr. 23, 2015, which is pending, which is a U.S. National Phase Application under 35 U.S.C. § 371 of International Patent Application No. PCT/US2013/031524, filed internationally on Mar. 14, 2013, which claims the benefit of U.S. Provisional Application No. 61/718,008, filed Oct. 24, 2012. The entire disclosure of each of the aforementioned related applications is hereby incorporated by reference.This invention was made with Government support under Grant ...

Novel tetrazines and method of synthezising the same

Provided herein, inter alia, are compositions and methods of synthesis and detection of tetrazines and diazonorcaradienes.

Enzymatic modification of nucleic acids

There are provided, inter alia, methods and reagents for labeling nucleic acids.

Functionalized 1,2,4,5-tetrazine compounds for use in bioorthogonal coupling reactions

The present application relates to functionalized 1,2,4,5-tetrazine compounds. The compounds are useful in compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reactions for the rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target.

TETRAZINE-CONTAINING COMPOUNDS AND SYNTHETIC METHODS THEREOF

Described herein are tetrazine derivatives and efficient synthetic methods of synthesis thereof using elimination-Heck cascade reaction. Provided herein is the synthesis of conjugated tetrazines from the tetrazine derivatives. Also provided herein are methods of use of the conjugated tetrazines as fluorogenic probes for live-cell imaging. 2. The method of claim 1 , wherein LG is an electron withdrawing group.3. The method of claim 1 , wherein:{'sub': 2', '2', '2', '2', '2', '2', '2, 'sup': +', '3A', '+', '3A', '+', '3B', '3C', '+', '3A', '3B', 'C', '+', '3A, 'LG is —N, —OR, —OSORF, a perfluoroalkylsulfonate, a tosylate, a mesylate, a halogen; —OH, —ONO, —OPO(OH), —ONO, —S(RR), —N(RRR), —OCOR, substituted or unsubstituted aryloxy or substituted or unsubstituted heteroaryloxy; and'}{'sup': 3A', '3B', '3C', '3B', '3C, 'sub': 3', '3', '3', '3', '2', '2', '2', '3', '4', '2', '2', '2', '2', '2', '2', '2', '3', '3', '3', '3', '2', '2', '2', '2, 'R, Rand Rare independently hydrogen, halogen, —CF, —CCl, —CBr, —CI, —OH, —NH, —COOH, —CONH, —NO, —SH, —SOH, —SOH, —SONH, —NHNH, —ONH, —NHC(O)NHNH, —NHC(O)NH, —NHSOH, —NHC(O)H, —NHC(O)—OH, —NHOH, —OCF, —OCCl, —OCBr, —OCI, —OCHF, —OCHC1, —OCHBr, —OCHI, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Rand Rsubstituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.'}4. The method of claim 1 , wherein the method further comprises a solvent.5. The method of claim 4 , wherein the solvent is an organic solvent.6. The method of claim 1 , wherein the method comprises an organic base.7. The method of claim 1 , wherein the method is conducted at a temperature of from about 25° C. to 200° C.8. The method of claim 1 , wherein the method is ...

Functionalized 1,2,4,5-tetrazine compounds for use in bioorthogonal coupling reactions

The present application relates to functionalized 1,2,4,5-tetrazine compounds. The compounds are useful in compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reactions for the rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target.

HIGHLY SENSITIVE DETECTION OF BIOMOLECULES USING PROXIMITY INDUCED BIOORTHOGONAL REACTIONS

There provided, inter alia, reagents and methods for modulation fluorescence of a tetrazine containing compound and/or a dienophile-containing compound. There is provided a method of detecting binding of a first affmity ligand and a second affinity ligand, the method includes the follow steps. Contacting a tetrazine-containing compound with a dienophile-containing compound, the tetrazine-containing compound comprising a first affinity ligand covalently attached to a tetrazine moiety and the dienophile-containing comprising a second affmity ligand covalently attached to a dienophile moiety. 1. A method of detecting binding of a first affinity ligand and a second affinity ligand , the method comprising(i) contacting a tetrazine-containing compound with a dienophile-containing compound, said tetrazine-containing compound comprising a first affinity ligand covalently attached to a tetrazine moiety and said dienophile-containing comprising a second affinity ligand covalently attached to a dienophile moiety;(ii) allowing said first affinity ligand to bind to said second affinity ligand or allowing said first affinity ligand and said second affinity ligand to bind to a third affinity ligand;(iii) allowing said tetrazine moiety to react with said dienophile moiety to form a pyridazine moiety within a detectable compound, said detectable compound comprising a fluorescent moiety rendered detectable upon formation of said pyridazine moiety.23.-. (canceled)4. The method of claim 1 , wherein said dienophile-containing compound comprises a fluorophore and said dienophile moiety is a vinyl ether functional group.5. The method of claim 4 , wherein said fluorophore is a xanthene claim 4 , a coumarin claim 4 , or a cyanine group claim 4 , wherein said xanthene group is a fluorescein or a rhodamine group.6. (canceled)8. The method of claim 7 , wherein:{'sup': 11', 'R', '13', '4', '15', 'R', '12', '13, 'sub': '3', 'Ris hydrogen, substituted or unsubsituted alkyl, or substituted or ...

Compositions and methods for delivering a substance to a biological target

The present application provides compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reaction for rapid and specific covalent delivery of a "payload" to a ligand bound to a biological target.

Compositions and methods for delivering a substance to a biological target

The present application provides compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reaction for rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target.

Compositions and methods for delivering a substance to a biological target

Compositions and methods for bioconjugation to quantum dots

The present disclosure provides for bio-orthoganl and modular conjugation methods for efficient coupling of organic compounds to quantum dots.

Compositions and methods for bioconjugation to quantum dots

The present disclosure provides for bio-orthoganl and modular conjugation methods for efficient coupling of organic compounds to quantum dots.

Enzymatic modification of nucleic acids

There are provided, inter alia, methods and reagents for labeling nucleic acids.

Compositions and methods for modifying dna

Provided herein are, inter alia, compositions and methods for modifying a DNA molecule. The methods include contacting a DNA molecule with a transglycosyl ase enzyme and a Pre-queuosinel (preQi) analog or derivative, wherein a guanine nucleobase within a hairpin structure in the DNA molecule is exchanged for the preQi analog or derivative.

Amphiphilic thiol compounds and uses thereof

Compositions and methods for modifying dna

Provided herein are, inter alia, compositions and methods for modifying a DNA molecule. The methods include contacting a DNA molecule with a transglycosylase enzyme and a Pre-queuosinel (preQi) analog or derivative, wherein a guanine nucleobase within a hairpin structure in the DNA molecule is exchanged for the preQi analog or derivative.

Methods and compositions for linking rna stem loops

Provided herein are, inter alia, methods and compositions for linking RNA stem loops. The methods include linking a first RNA stem loop and a second RNA stem loop by way of a preQ1 linking compound.

Depalmitoylating compositions and the use thereof

Disclosed herein, inter alia , are depalmitoylating compounds, compositions, and methods of use thereof.

Tetrazines and method of synthezising the same

Provided herein, inter alia, are compositions and methods of synthesis and detection of tetrazines, e.g., a tetrazine of formula and diazonorcaradienes.

Depalmitoylating compositions and the use thereof

Disclosed herein, inter alia , are depalmitoylating compounds, compositions, and methods of use thereof.

Functionalized 1,2,4,5-tetrazine compounds for use in bioorthogonal coupling reactions

The present application relates to functionalized 1,2,4,5-tetrazine compounds. The compounds are useful in compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reactions for the rapid and specific covalent delivery of a “payload” to a ligand bound to a biological target.