title: Synthesis of di- and tri-saccharide fragments of Salmonella typhi Vi capsular polysaccharide and their zwitterionic analogues.
abstract: Zwitterionic polysaccharides (ZPS) behave like traditional T cell-dependent antigens, suggesting the design of new classes of vaccines alternative to currently used glycoconjugates and based on the artificial introduction of a zwitterionic charge motif onto the carbohydrate structure of pathogen antigens. Here we report the new synthesis and antigenic evaluation of di-/tri-saccharide fragments of Salmonella typhi Vi polysaccharide, as well as of their corresponding zwitterionic analogues. Our strategy is based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approach using disaccharide donors. The effect of structural modifications of the synthetic compounds on antigenic properties was evaluated by competitive ELISA. All the oligosaccharides were recognized by specific anti-Vi polyclonal antibodies in a concentration-dependent manner, and the introduction of a zwitterionic motif into the synthetic molecules did not prevent the binding.
authors.affiliation: Department of Chemistry and CRC Materiali Polimerici (LaMPo), University of Milan, Via Golgi 19, 20133 Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fusari
authors.affiliation: Department of Pharmaceutical Sciences, University of 'Piemonte Orientale, A. Avogadro', Largo Donegani 2, Novara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fallarini
authors.affiliation: Department of Pharmaceutical Sciences, University of 'Piemonte Orientale, A. Avogadro', Largo Donegani 2, Novara, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Department of Chemistry and CRC Materiali Polimerici (LaMPo), University of Milan, Via Golgi 19, 20133 Milan, Italy. Electronic address: luigi.lay@unimi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Lay
mesh_terms: D000606:Amino Sugars / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006736:Horses; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology; D012485:Salmonella typhi; D013329:Structure-Activity Relationship; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology
chemical_list: D000606:Amino Sugars; D000906:Antibodies; D004187:Disaccharides; D011135:Polysaccharides, Bacterial; D014312:Trisaccharides; C054154:capsular polysaccharide, Salmonella
keywords: Glycoconjugate vaccines; Glycosylation; Salmonella typhi; Vi antigen; Zwitterionic polysaccharides