title: Synthesis of Staphylococcus aureus type 5 capsular polysaccharide repeating unit using novel L-FucNAc and D-FucNAc synthons and immunochemical evaluation.
abstract: Staphylococcus aureus is a major cause of nosocomial infections. Glycoconjugates of type 5 and 8 capsular polysaccharides have been investigated for vaccine application. The proposed structure of type 5 polysaccharide is: →4-β-D-ManNAcA-(1→4)-α-L-FucNAc(3OAc)-(1→3)-β-D-FucNAc-(1→. The stereocontrolled insertion of these three glycosydic bonds is a real synthetic challenge. In the present paper we report the preparation of two novel versatile L- and D-fucosamine synthons from commercially available starting materials. In addition we applied the two building blocks to the synthesis of type 5 trisaccharide repeating unit. The immunochemical properties of the synthesized trisaccharide were assessed by competitive ELISA and by immunodot blot analysis using sera of mice immunized with type 5 polysaccharide conjugated to CRM(197). The results suggest that although the type 5 S. aureus trisaccharide is recognized by specific anti polysaccharide antibodies in dot blot, structures longer than the trisaccharide may be needed in order to significantly compete with the native type 5 polymer in the binding with sera from mice immunized with S. aureus type 5 polysaccharide-CRM(197) conjugate.
authors.affiliation: Research Center, Novartis Vaccine and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Danieli
authors.forename: Daniela
authors.initials: D
authors.lastname: Proietti
authors.forename: Giulia
authors.initials: G
authors.lastname: Brogioni
authors.forename: Maria R
authors.initials: MR
authors.lastname: Romano
authors.forename: Emilia
authors.initials: E
authors.lastname: Cappelletti
authors.forename: Marta
authors.initials: M
authors.lastname: Tontini
authors.forename: Francesco
authors.initials: F
authors.lastname: Berti
authors.forename: Luigi
authors.initials: L
authors.lastname: Lay
authors.forename: Paolo
authors.initials: P
authors.lastname: Costantino
authors.forename: Roberto
authors.initials: R
authors.lastname: Adamo
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions; D016667:Bacterial Capsules / Q000737:chemistry* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005643:Fucose / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D007120:Immunochemistry; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D014574:Uronic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology
chemical_list: D011135:Polysaccharides, Bacterial; D014574:Uronic Acids; C054106:capsular polysaccharide, type 5, Staphylococcus aureus; D005643:Fucose