Synthetic functional mimics of the O-antigen from Shigella flexneri 2a are seen as promising vaccine components against endemic shigellosis. Herein, the influence of the polysaccharide non-stoichiometric di-O-acetylation on antigenicity is addressed for the first time. Three decasaccharides, representing relevant internal mono- and di-O-acetylation profiles of the O-antigen, were synthesized from a pivotal protected decasaccharide designed to tailor late stage site-selective O-acetylation. The latter was obtained via a convergent route involving the imidate glycosylation chemistry. Binding studies to five protective mIgGs showed that none of the acetates adds significantly to broad antibody recognition. Yet, one of the five antibodies had a unique pattern of binding. With IC50 in the micromolar to submicromolar range mIgG F22-4 exemplifies a remarkable tight binding antibody against diversely O-acetylated and non-O-acetylated fragments of a neutral polysaccharide of medical importance.
synthesis, chemistry, functional, polysaccharide, O-antigen, O antigen, Shigella flexneri, antibodies, antibody, recognition, neutral, O-specific, O-specific polysaccharide, O-acetylation, Shigella, fragment, component, time, binding, glycosylation, vaccine, Synthetic, protective, antigenicity, PDF, France, medical, influence, pattern, importance, profile, acetate, Acetates, biomolecule
NCBI PubMed ID: 24836582Publication DOI: 10.1039/c3ob42586jJournal NLM ID: 101154995Publisher: The Royal Society of Chemistry
Correspondence: laurence.mulard@pasteur.fr
Institutions: INSERM U786, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France, Institut Pasteur, Chimie des Biomolécules, Dépt de Biologie Structurale et Chimie, 28 rue du Dr Roux, 75724 Paris Cedex 15, France, CNRS UMR 3523, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France, Univ. Paris Descartes Sorbonne Paris Cité, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France, Institut Pasteur, RMN des Biomolécules, Dépt de Biologie Structurale et Chimie, 28 rue du Dr Roux, 75015 Paris, France, CNRS UMR 3528, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France, Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert Roessle Strasse 10, 13125 Berlin, Germany, Institut Pasteur, Pathogénie Microbienne Moléculaire, Dépt de Biologie Cellulaire et Infection, 28 rue du Dr Roux, 75015 Paris, France, Institut Pasteur, Plate-forme d'Ingénierie des Anticorps, Dépt de Biologie Structurale et Chimie, 25 rue du Dr Roux, 75015 Paris, France
Methods: 13C NMR, 1H NMR, chemical methods, RP-HPLC, ESI-TOF-MS, chemical syhtnesis
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