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A General Strategy for the Chemoenzymatic Synthesis of Asymmetrically Branched N-Glycans

Science  26 Jul 2013:
Vol. 341, Issue 6144, pp. 379-383
DOI: 10.1126/science.1236231

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Sweet Variety

Proteins fold into a great variety of shapes—but, topologically, they always start as a more or less straight line of linked amino acids. In contrast, carbohydrates manifest a range of structures in which the sugar building blocks connect through multiple branch points. Wang et al. (p. 379, published online 26 July; see the Perspective by Kiessling and Kraft) designed a versatile precursor that could be transformed into many different branched glycans with distinct building blocks along each branch.

Abstract

A systematic, efficient means of producing diverse libraries of asymmetrically branched N-glycans is needed to investigate the specificities and biology of glycan-binding proteins. To that end, we describe a core pentasaccharide that at potential branching positions is modified by orthogonal protecting groups to allow selective attachment of specific saccharide moieties by chemical glycosylation. The appendages were selected so that the antenna of the resulting deprotected compounds could be selectively extended by glycosyltransferases to give libraries of asymmetrical multi-antennary glycans. The power of the methodology was demonstrated by the preparation of a series of complex oligosaccharides that were printed as microarrays and screened for binding to lectins and influenza-virus hemagglutinins, which showed that recognition is modulated by presentation of minimal epitopes in the context of complex N-glycans.

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