Chemical Synthesis and Immunological Evaluation of Helicobacter pylori Serotype O6 Tridecasaccharide O-Antigen Containing a Unique DD-Heptoglycan.

The development of glycoconjugate vaccines against Helicobacter pylori is challenging. An exact epitope of the H. pylori lipo-polysaccharide (LPS) O-antigens that contain Lewis determinant oligosaccharides and unique dd-heptoglycans has not yet been identified. Reported here is the first total synthesis of H. pylori serotype O6 tridecasaccharide O-antigen containing a terminal Le(y) tetrasaccharide, a unique alpha-(1 -> 3)-, alpha-(1 -> 6)-, and alpha-(1 -> 2)-linked heptoglycan, and a beta-d-galactose connector, by an [(2x1)+(3+8)] assembly sequence. Seven oligosaccharides covering different portions of the entire O-antigen were prepared for immunological investigations with a particular focus on elucidation of the roles of the dd-heptoglycan and Le(y) tetrasaccharide. Glycan microarray analysis of sera from rabbits immunized with isolated serotype O6 LPS revealed a humoral immune response to the alpha-(1 -> 3)-linked heptoglycan, a key motif for designing glycoconjugate vaccines for H. pylori serotype O6.