A synthetic glycan array containing Cryptococcus neoformans glucuronoxylomannan capsular polysaccharide fragments allows the mapping of protective epitopes.

Chemical Science
Lorenzo GuazzelliStefan Oscarson

Abstract

A convergent synthetic strategy to Cryptococcus neoformans glucuronoxylomannan (GXM) capsular polysaccharide part structures was developed based on di-, tri-, tetra-, penta- and hexasaccharide thioglycoside building blocks. The approach permitted the synthesis of a library of spacer-containing serotype A and D related GXM oligosaccharide structures, ranging from di- to octadecasaccharides. Ten deprotected GXM compounds (mono- to decasaccharide) were printed onto microarray plates and screened with seventeen mouse monoclonal antibodies (mAbs) to GXM. For the first time a GXM oligosaccharide structure (a serotype A decasaccharide), capable of being recognized by neutralizing forms of these GXM-specific mAbs, has been identified, offering insight into the binding epitopes of a range of protective monoclonal antibodies and furthering our efforts to develop semi-synthetic conjugate vaccine candidates against C. neoformans.

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Citations

Jan 31, 2021·Proceedings of the National Academy of Sciences of the United States of America·Conor J CrawfordStefan Oscarson
Apr 22, 2021·The Biochemical Journal·J Sebastian TemmeJeffrey C Gildersleeve
Jul 27, 2021·Organic Process Research & Development·Conor J CrawfordShuai Chen

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Methods Mentioned

BETA
nuclear magnetic resonance
acetylation
glycosylation
glycosylations
reversed phase chromatography

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