Glycopeptide Synthesis through endo-Glycosidase-Catalyzed Oligosaccharide Transfer of Sugar Oxazolines:Probing Substrate Structural Requirement

摘要

An array of sugar oxazolines was synthesized and tested as donor substrates for the Arthrobacter endo-beta-N-acetylglucosaminidase (Endo-A)-cat-alyzed glycopeptide synthesis.The experiments revealed that the minimum structure of the donor substrate required for Endo-A catalyzed transgly-cosylation is a Man betal->4-GlcNAc oxa-zoline moiety.Replacement of the beta-D-Man moiety with beta-D-Glc,beta-D-Gal,and beta-D-GlcNAc monosaccharides resulted in the loss of substrate activity for the disaccharide oxazoline.Despite this,the enzyme could tolerate modifications such as attachment of additional sugar residues or a functional group at the 3- and/or 6-positions of the beta-D-Man moiety,thus allowing a successful transfer of selectively modified oligo-saccharides to the peptide acceptor.On the other hand,the enzyme has a great flexibility for the acceptor portion and could take both small and large GlcNAc-peptides as the acceptor.The studies implicate a great potential of the endoglycosidase-catalyzed transgly-cosylation for constructing both natural and selectively modified glycopeptides.