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RSC GXM to submit-1.pdf (1.12 MB)

A Synthetic Glycan Array Containing Cryptococcus Neoformans Glucuronoxylomannan Capsular Polysaccharide Fragments Allows the Mapping of Protective Epitopes

preprint
submitted on 28.02.2020, 17:31 and posted on 02.03.2020, 13:09 by Lorenzo Guazzelli, Rebecca Ulc, Anthony Bowen, Conor Crawford, Orla McCabe, Anne J. Jedlicka, Maggie P. Wear, Arturo Casadevall, Stefan Oscarson
A block synthetic strategy to Cryptococcus neoformans glucuronoxylomannan (GXM) capsular polysaccharide part structures has been 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 GXMspecific 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.

History

Email Address of Submitting Author

stefan.oscarson@ucd.ie

Institution

University College Dublin

Country

Ireland

ORCID For Submitting Author

0000-0002-8273-4918

Declaration of Conflict of Interest

None

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