Chemical Synthesis Elucidates the Immunological Importance of a Pyruvate Modification in the Capsular Polysaccharide of Streptococcus pneumoniae Serotype 4.

Angew Chem Int Ed Engl. 2015 Jul 24. doi: 10.1002/anie.201504847. [Epub ahead of print]

Chemical Synthesis Elucidates the Immunological Importance of a Pyruvate Modification in the Capsular Polysaccharide of Streptococcus pneumoniae Serotype 4.

Pereira CL1,2, Geissner A3,4, Anish C3,4, Seeberger PH5,6.

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Abstract

Carbohydrate modifications are believed to strongly affect the immunogenicity of glycans. Capsular polysaccharides (CPS) from bacterial pathogens are frequently equipped with a pyruvate that can be placed across the 4,6-, 3,4-, or 2,3-positions. A trans-2,3-linked pyruvate is present on the CPS of the Gram-positive bacterium Streptococcus pneumoniae serotype 4 (ST4), a pathogen responsible for pneumococcal infections. To assess the immunological importance of this modification within the CPS repeating unit, the first total synthesis of the glycan was carried out. Glycan microarrays containing a series of synthetic antigens demonstrated how antibodies raised against natural ST4 CPS specifically recognize the pyruvate within the context of the tetrasaccharide repeating unit. The pyruvate modification is a key motif for designing minimal synthetic carbohydrate vaccines for ST4.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

Streptococcus pneumoniae; antigens; oligosaccharides; pyruvate acetal; synthetic vaccines

PMID: 26212109 [PubMed - as supplied by publisher]