Extended sugar-assisted glycopeptide ligations: development, scope, and applications.

摘要: Recently, we reported the development of sugar-assisted ligation (SAL), a novel peptide method for synthesis glycopeptides. After screening large number glycoprotein sequences in database, it became evident that proportion (approximately 53%) O-glycosylation sites contain amino acid residues will not undergo SAL reactions. To overcome these inherent limitations and broaden scope report here an extended method. Glycopeptides containing up to six extensions N-terminal glycosylated residue were shown facilitate reactions with thioesters, products isolated good yields. Kinetic analysis was used show as glycopeptides by further residues, slower. This finding rationalized molecular dynamics simulations using AMBER9. These studies suggested general trend whereby proximal distance between reactive thioester intermediate (the amine carbonyl carbon thioester) increased extended, thus slowing down rate. Each methods showed broad tolerance different combinations at junction. Re-evaluation database 95% O-linked glycosylation can now be utilized or As such, this represents extremely valuable tool naturally occurring glycoproteins. demonstrate applicability method, successfully implemented starting unit cancer-associated MUC1 glycoprotein.