title: Synthesis and immunochemical evaluation of a non-methylated disaccharide analogue of the anthrax tetrasaccharide.
abstract: Anthrax tetrasaccharide is an oligosaccharide expressed at the outermost surface of the Bacillus anthracis spores, featuring three rhamnoses and a rare sugar called anthrose. This motif has now been identified as a plausible component of future human vaccines against anthrax. We report herein the synthesis of a 2-O-demethylated-β-D-anthropyranosyl-(1→3)-α-L-rhamnopyranose disaccharide analogue of this tetrasaccharide from a cyclic sulfate intermediate. This disaccharide conjugated to BSA induces an anti-native tetrasaccharide IgG antibody response when administered in BALB/c mice. Moreover, induced sera bound to native B. anthracis endospores. These results suggest that the disaccharide analogue, easily amenable for a synthetic scale-up, could be used in a glycoconjugate antigen formulation.
authors.affiliation: Laboratoire des Glucides, FRE CNRS 3517, Institut de Chimie de Picardie, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens Cedex, France.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Milhomme
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Köhler
authors.forename: David
authors.initials: D
authors.lastname: Ropartz
authors.forename: David
authors.initials: D
authors.lastname: Lesur
authors.forename: Serge
authors.initials: S
authors.lastname: Pilard
authors.forename: Florence
authors.initials: F
authors.lastname: Djedaïni-Pilard
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Beyer
authors.forename: Cyrille
authors.initials: C
authors.lastname: Grandjean
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use*; D001408:Bacillus anthracis / Q000737:chemistry / Q000276:immunology*; D002417:Cattle; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000031:analogs & derivatives* / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D013171:Spores, Bacterial / Q000737:chemistry / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D004187:Disaccharides; D006001:Glycoconjugates; D011135:Polysaccharides, Bacterial; D012710:Serum Albumin, Bovine