Postligation-desulfurization: A general approach for chemical protein synthesis

Abstract

Native chemical ligation, involving regioselective and chemoselective coupling of two unprotected peptide segments, enabled the synthesis of polypeptide withmore than 200 amino acids. However, cysteinewas indispensable in this synthetic technique in its initial format, which limited its further application. Thus, considerable effort has been put into breaking the restriction of cysteine-containing ligation. As a consequence, postligation-desulfurization, concerning thiol-mediated ligation followed by desulfurization, was developed. This review describes the development and recent progress on the chemical synthesis of peptides and proteins encompassing postligation-desulfurization at alanine, valine, lysine, threonine, leucine, proline, arginine, aspartic acid, glutamate, phenylalanine, glutamine, and tryptophan.