The present invention relates to a method for prolonging half-life of a protein or a (poly)peptide by replacing one or more amino acid residues of the protein. Further, the present invention is about the protein having a prolonged half-life prepared by the method above.

The present invention relates to a method for prolonging half-life of a protein or a (poly)peptide by replacing one or more amino acid residues of the protein. Further, the present invention is about the protein having a prolonged half-life prepared by the method above.

The present invention relates to a method for prolonging half-life of a protein or a (poly)peptide by replacing one or more amino acid residues of the protein. Further, the present invention is about the protein having a prolonged half-life prepared by the method above.

The present invention relates to a method for covalently binding a first agent and a second agent, the first agent comprising a first recognition element, wherein the first recognition element comprises an 1,4-dioxo moiety having a structure of Formula IA, IB or IC, wherein R.sup.12 is C.sub.1-30alkyl, C.sub.2-30alkenyl, C.sub.6-15aryl, or C.sub.5-15heteroaryl, wherein the C.sub.1-30alkyl, C.sub.2-30alkenyl, C.sub.6-15aryl, or C.sub.5-15heteroaryl group are optionally substituted with an C.sub.1-6alkyl, C.sub.3-6cycloalkyl, halogen, amine, hydroxyl, sulfhydryl, carboxyl, or C.sub.1-6alkoxy; and R.sup.13, if present, is hydrogen, C.sub.1-30alkyl or C.sub.2-30alkenyl; the second agent comprising a second recognition element, wherein the second recognition element comprises a nucleophilic moiety selected from a hydrazine moiety, an aminooxy moiety, an aminosulfanyl moiety or a hydroxylamine moiety; wherein: (A) the first recognition element and the second recognition element are capable of non-covalently binding to each other such that the 1,4-dioxo moiety and the nucleophilic moiety are brought in proximity; the method comprising contacting the first agent with the second agent, thereby covalently binding the 1,4-dioxo moiety and the nucleophilic moiety; or (B) the first recognition element and the second recognition element are capable of non-covalently binding to a third recognition element such that the 1,4-dioxo moiety and the nucleophilic moiety are brought in proximity; the method comprising contacting the first agent with the second agent and the third recognition element, thereby covalently binding the 1,4-dioxo moiety and the nucleophilic moiety; wherein the first recognition element is a peptide nucleic acid (PNA), a peptide, a peptidomimetic, an oligonucleotide, an oligonucleotide mimic, or a combination thereof; the second recognition element is a PNA, a peptide, a peptidomimetic, an oligonucleotide, an oligonucleotide mimic, or a combination thereof; and the third recognition element is a nucleic acid, an oligonucleotide, an oligonucleotide mimic, a PNA, a protein, a peptide, a cyclodextrin, a cucurbituril, a cyclophane, or a combination thereof. The invention further provides related products including kits of parts.

A method for preparing AMG 416, or a pharmaceutically acceptable salt thereof, is provided.

The present invention provides means and methods for equipping a polypeptide of interest at its C-terminus with a versatile adaptor amino acid that allows the functionalization of the polypeptide of interest.

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.

In one aspect, the present disclosure provides a system and method for the identification and characterization of a transglutaminase. Further, the present disclosure provides transglutaminase enzymes for forming isopeptide bonds, methods of forming isopeptide bonds in the presence of transglutaminases, and substrate tags for use with transglutaminases. In another aspect, the present disclosure provides glutamine-containing substrates (or Q-tag substrates) that are more resistant to proteases/clipping and therefore, more stable, than other Q-tag substrates, and their uses in substrate tags for cross-linking to an amine-donor tag via an isopeptide bond mediated by a microbial transglutaminase.

According to one aspect, the present disclosure provides a method of identifying a substrate of a transglutaminase using a peptide array comprising a plurality of peptides. The method includes the steps of contacting the peptides in the peptide array with the transglutaminase, allowing the transglutaminase to bind to the peptides, and identifying the substrate of the transglutaminase.

A multifunctional chemical agents comprising functional agents Fn1, Fn2 and linkers, for the linchpin directed (LDM), protein directed (PDPM) modifications of proteins, and Fn1 accelerated kinetic labeling by Fn2.