Chemical and chemoenzymatic synthesis of glycosyl-amino acids and glycopeptides related to Trypanosoma cruzi mucins

Campo, Vanessa Leiria; Carvalho, Ivone; Allman, Sarah; Davis, Benjamin G. and Field, Robert A. (2007). Chemical and chemoenzymatic synthesis of glycosyl-amino acids and glycopeptides related to Trypanosoma cruzi mucins. Organic & Biomolecular Chemistry, 5(16) pp. 2645–2657.

DOI: https://doi.org/10.1039/b707772f

Abstract

This study describes the synthesis of the α-and β-linked N-acetyllactosamine (Galp-β-1,4-GlcNAc; LacNAc) glycosides of threonine (LacNAc-Thr). LacNAc-α-Thr was prepared by direct chemical coupling of a 2-azido-2-deoxy-lactose disaccharide donor to a suitable partially protected threonine unit. In contrast, stepwise chemical generation of β-linked N-acetylglucosamine followed by enzymatic galactosylation to give LacNAc-β-Thr proved effective, whereas use of a 2-azido-2-deoxy-lactose donor in acetonitrile failed to give the desired β-linked disaccharyl glycoside. This study illustrates that it is possible to overcome the inherent stereoselection for 1,2-trans chemical glycosylation with a GlcNAc donor, and that the well-established preference of bovine β-1,4-galactosyltransferase for β-linked acceptor substrates can also be overcome. Using this knowledge, short glycopeptide fragments based on T. cruzi mucin sequences, Thr-Thr-[LacNAcThr]-Thr-Thr-Gly, were synthesised. All LacNAc-based compounds outlined were shown to serve as acceptor substrates for sialylation by T. cruzi trans-sialidase.

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