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

被引：47
作者：
Campo, Vanessa Leiria [1 ,2 ]
Carvalho, Ivone [2 ]
Allman, Sarah [3 ]
Davis, Benjamin G. [3 ]
Field, Robert A. [1 ,4 ]
机构：
[1] School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich
[2] Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo
[3] Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, OX1 3TA, Mansfield Road
[4] Department of Biological Chemistry, John Innes Centre, Norwich, NR4 7UH, Colney Lane
来源：
Organic and Biomolecular Chemistry | 2007年 / 5卷 / 16期
基金：
英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词：
D O I：
10.1039/b707772f
中图分类号：
学科分类号：
摘要：
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. © The Royal Society of Chemistry.
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页码：2645 / 2657
页数：12
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