Regioselective Glycosylation Strategies for the Synthesis of Group Ia and Ib Streptococcus Related Glycans Enable Elucidating Unique Conformations of the Capsular Polysaccharides

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.B oth are composed of the same monosaccharide residues and differ only in the connection of the Neu5Aca2-3Gal side chain to the GlcNAc unit, which is a b1-4 linkage in serotype Ia and a b1-3 linkage in serotype Ib. The developmento fe fficient regioselective routes for GlcNAcb1-3[Glcb1-4]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 Neu5Aca2-3Gal moieties on the polysaccharide backbones and ah igherf lexibility of Ib polymer relative to Ia, which can impact epitope exposure.[b] Dr.I .C alloni, Dr.A .Ardµ,P rof. J.Supporting information (containingt he experimental procedures for the synthesis of oligosaccharides 1-5 and their characterization, molecular dynamicss imulations, and NMR spectra)and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.

Structure‐Guided Design of a Group B Streptococcus Type III Synthetic Glycan–Conjugate Vaccine

“…Therefore, the trisaccharide acceptor 3 , was glycosylated with the known lactose bromide donor 2 having a participating ester at position 2 of the Glc unit, and an orthogonal isopropylidene protection at the 3,4‐hydroxyls of the Gal residue . After acid mediated isopropylidene removal, the pentasaccharide 5 was subjected to a regioselective glycosylation at Gal C‐3 with donor 6 , according to a recent protocol we have developed, to give the protected hexasaccharide 7 . Deprotection was carried out through sequential reactions: 1) hydrolysis of the methyl ester with lithium iodide in pyridine; 2) N ‐phthalimide removal with ethylenediamine followed by acetylation of the generated amine; 3) methanolysis of the acyl esters and 4) Pd‐charcoal catalyzed hydrogenation to obtain the target glycan 1 .…”

Chemical Synthesis and Immunological Evaluation of Fragments of the Multiantennary Group-Specific Polysaccharide of Group B Streptococcus

“… 14 − 16 , 23 − 29 The generation of well-defined oligosaccharide fragments also allows for binding studies (for example with monoclonal antibodies) at the atomic level and the mapping of relevant epitopes. Chemical syntheses of the repeating units of serotypes Ia, 30 − 32 Ib, 32 II, 33 III, 34 and V, 35 have been published in the last 10 years. As GBC is isolated as a contaminant from GBS CPS, the availability of pure and well-defined GBC structures is critical to elucidate its immunological potential.…”

Semi- and fully synthetic carbohydrate vaccines against pathogenic bacteria: recent developments

“…Since 2016, several synthetic methods for the oligosaccharide repeating units of GBS CPS were published: [ 1 ] a dimer of the branched polysaccharide from ST Ia [ 53 ]; (2) regioselective routes to building blocks that accessed the ST Ia and Ib repeating units [ 58 ]; (3) the synthesis of three different pentasaccharide frameshifts of ST III [ 54 ] that were later investigated as a decasaccharide fragment composed of two repeating units to reveal the portion necessary for antibody recognition [ 56 ]; (4) a branched heptasaccharide of the repeating unit of ST II [ 59 ]; (5) ST V [ 60 ]; and (6) a hexasaccharide repeating unit with the dimer of this repeating unit from ST VII [ 61 ]. A dimer of the branched pentasaccharide repeating unit from ST Ia and its corresponding monomer conjugated to CRM 197 resulted in robust antibody response in mice [ 53 ].…”