Highly Efficient Endoglycosidase-Catalyzed Synthesis of Glycopeptides Using Oligosaccharide Oxazolines as Donor Substrates

Abstract

A highly efficient chemoenzymatic synthesis of N-glycopeptides was achieved. It was found that using synthetic oligosaccharide oxazolines, the mimics of the presumed oxazolinium ion intermediate formed in a retaining mechanism of substrate-assisted catalysis, as the donor substrates and GlcNAc-peptides as the acceptors, the endo-beta-N-acetylglucosaminidase (ENGase)-catalyzed transglycosylation gave a high yield (73-82%) of the corresponding glycopeptides in a regio- and stereospecific manner, regardless of the size of the peptide portions. The use of the oligosaccharide oxazolines as donor substrates not only expanded the substrate availability but also led to a substantial enhancement of the synthetic efficiency, compared to the use of natural N-glycans.