Synthesis of di- and tri-saccharide fragments of Salmonella typhi Vi capsular polysaccharide and their zwitterionic analogues. Issue 23 (1st December 2015)

• Record Type: Journal Article
• Authors: Fusari, Matteo; Fallarini, Silvia; Lombardi, Grazia; Lay, Luigi
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 23(2015)
• Page Start: 7439
• Page End: 7447
• Publication Date: 2015-12-01
• Subjects: Glycoconjugate vaccines -- Zwitterionic polysaccharides -- Salmonella typhi -- Vi antigen -- Glycosylation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.10.043
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.