Abstract
Group B Streptococcus serotypes Ia and Ib capsular polysaccharides are key targets for vaccine development. In spite of their immunospecifity these polysaccharides share high structural similarity. Both are composed of the same monosaccharide residues and differ only in the connection of the Neu5Acα2‐3Gal side chain to the GlcNAc unit, which is a β1‐4 linkage in serotype Ia and a β1‐3 linkage in serotype Ib. The development of efficient regioselective routes for GlcNAcβ1‐3[Glcβ1‐4]Gal synthons is described, which give access to different group B Streptococcus (GBS) Ia and Ib repeating unit frameshifts. These glycans were used to probe the conformation and molecular dynamics of the two polysaccharides, highlighting the different presentation of the protruding Neu5Acα2‐3Gal moieties on the polysaccharide backbones and a higher flexibility of Ib polymer relative to Ia, which can impact epitope exposure.
Highlights
Group B Streptococcus (GBS) is a leading cause of pneumonia, sepsis, meningitis, and death in neonates.[1]
Faster and efficient access to a GlcNAcb1-3Gal disaccharide building block plays a central role to obtain the trisaccharide acceptor without a temporary protection at position 4 for further assembly of GBS capsular polysaccharides (CPSs) in exo-anti-F (Ia) fragments
To achieve its regioselective synthesis, we investigated the effect of arming benzyl and disarming benzoyl groups[22,23] at position 2 and 6 of the Gal acceptors in tuning the reactivity of the 3- and 4-OH, respectively, in combination with various protecting and leaving groups in the glucosamine donors
Summary
The latter pentasaccharides 3 and 4 share identical monosaccharide composition with milk oligosaccharides, which have recently been proposed to inhibit GBS colonization.[10] The availability of well-defined GBS CPS glycans is key to explore interactions with serotype-specific monoclonal antibodies in order to identify relevant glycoepitopes for elucidating the mechanism of action of the polysaccharide conjugates and for the development of synthetic carbohydratebased vaccines.[11] The most studied of GBS polysaccharides is type III. Combination of NMR data from the synthetic GBS CPS Ia and Ib repeating units in their branched form 1 and 3, respectively, and molecular dynamics simulation allowed to shed light on how the variation of a single sugar connection dramatically affects the conformational properties of CPS Ia and Ib polysaccharides, and exposition of potential epitopes for antibody recognition
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