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: Ophélie Milhomme, Susanne M Köhler, David Ropartz, David Lesur, Serge Pilard, Florence Djedaïni-Pilard, Wolfgang Beyer, Cyrille Grandjean
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 10 Issue 42 Pg. 8524-32 (Nov 14 2012) ISSN: 1477-0539 [Electronic] England
• PMID: 23010801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthrax Vaccines
• Disaccharides
• Glycoconjugates
• Polysaccharides, Bacterial
• Serum Albumin, Bovine

Topics

• Animals
• Anthrax (immunology, microbiology, prevention & control)
• Anthrax Vaccines (chemical synthesis, chemistry, immunology, therapeutic use)
• Bacillus anthracis (chemistry, immunology)
• Cattle
• Disaccharides (chemical synthesis, chemistry, immunology, therapeutic use)
• Female
• Glycoconjugates (chemical synthesis, chemistry, immunology, therapeutic use)
• Humans
• Immunization
• Mice
• Mice, Inbred BALB C
• Polysaccharides, Bacterial (analogs & derivatives, immunology)
• Serum Albumin, Bovine (chemical synthesis, chemistry, immunology, therapeutic use)
• Spores, Bacterial (chemistry, immunology)