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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: bacillary dysentery (shigellosis) [ICD11: 1A02

, ICD11: SA56

, ICD11: XN7HG

]; infection due to Shigella flexneri [ICD11: XN7Y2

]

The structure was elucidated in this paper
NCBI PubMed ID: 24836582
Publication DOI: 10.1039/c3ob42586j
Journal NLM ID: 101154995
Publisher: 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

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

Structure type: oligomer
Location inside paper: p.4220, scheme 1, 1, p.4223, scheme 5, 1
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_120354,IEDB_125613,IEDB_125614,IEDB_133753,IEDB_133754,IEDB_135807,IEDB_135808,IEDB_135809,IEDB_135813,IEDB_135817,IEDB_135849,IEDB_136105,IEDB_137340,IEDB_141807,IEDB_141815,IEDB_142488,IEDB_143253,IEDB_144998,IEDB_146664,IEDB_151531,IEDB_153213,IEDB_225177,IEDB_227868,IEDB_227871,IEDB_885823,IEDB_983931,SB_192

Methods: 13C NMR, 1H NMR, chemical methods, RP-HPLC, ESI-TOF-MS, chemical syhtnesis
Biological activity: the influence on Ab recognition of non-stoichiometric O-acetylation and/or multiple O-acetylations at various sites within one repeat of a given polysaccharide
Synthetic data: chemical
Comments, role: synthetic product

Related record ID(s): 30059, 30240, 30241, 30242
NCBI Taxonomy refs (TaxIDs): 42897
Show glycosyltransferases

NMR conditions: in D2O

¹H NMR data: present in publication

¹³C NMR data: present in publication

There is only one chemically distinct structure:

CC(=O)N[C@H]1[C@H](O[C@H]2[C@H](O[C@H]3[C@H](O[C@@H]4[C@@H](O[C@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)[C@H](C)O[C@@H](O[C@H]5[C@H](O)[C@@H](CO)O[C@@H](OCCN)[C@@H]5NC(C)=O)[C@@H]4O)O[C@@H](C)[C@H](O)[C@H]3O)O[C@@H](C)[C@H](O)[C@H]2OC(C)=O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@@H]1O[C@@H](C)[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@@H](O)[C@H]2O[C@@H]2O[C@@H](C)[C@H](O)[C@@H](O)[C@H]2O)[C@H]1O

SVG MW SMILES 3D mol Ionize