A new strategy for the chemoenzymatic synthesis of glycopeptides by De-O-acetylation with an esterase and glycosylations with glycosyltransferases

Abstract

Glycopeptides are fragments of glycoproteins and are important in evaluating the biological roles of carbohydrates in glycoproteins. Fmoc solid-phase peptide synthesis using acetyl-protected glycosylated amino acids is a common strategy for the preparation of glycopeptides, but this approach normally requires chemical de-O-acetylation with a base that β-eliminates sugar residues and epimerizes the peptide backbone. Here we demonstrate a facile new chemoenzymatic synthetic strategy for glycopeptides, using an esterase for the de-O-acetylation of sugar residues and glycosyltransferases for successive sugar elongations at neutral pH.

Keywords: Chemoenzymatic synthesis; De-O-acetylation; Esterase; Glycopeptides; Glycosyltransferase.