Abstract: The invention is directed to methods and compositions for chemical ligation of a first component that includes a carboxythioester and a second component that includes an amino-functionalized compound bearing a branched side chain that includes a removable thiol auxiliary, to give a ligation product having an amide bond at the ligation site. The reactants of the invention are chemoselective and the thiol moiety is removable from the ligation product. Removal of the thiol can be exploited to generate a native side chain at the ligation site. The methods and compositions of the invention are particularly useful for ligation of peptides and polypeptides. The ligation system of the invention is applicable to a wide variety of molecules, and thus can be exploited to generate peptides, polypeptides and other amino acid containing polymers.

Abstract: The present invention provides methods of assembling oligopeptides or polypeptides in a native chemical ligation reaction that eliminates the formation of unwanted side products resulting from the presence of an unprotecte acidic C-terminal oligopeptide thioester. An important aspect of the present invention is providing side chain protected acidic C-terminal oligopeptide thioesters.