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Helicobacter pylori, Immunology, O-antigen, Total synthesis, tridecasaccharide
Abstract:
The development of glycoconjugate vaccines against Helicobacter pylori is challenging. An exact epitope of the H. pylori lipopolysaccharides (LPS) O-antigens that contain Lewis determinant oligosaccharides and unique DD-heptoglycans has not yet been identified. Here, we report the first total synthesis of H. pylori serotype O6 tridecasaccharide O-antigen containing a terminal Ley tetrasaccharide, a unique α-(1→3)-, α-(1→6)- and α-(1→2)-linked heptoglycan, and a ?-D-galactose connector through an [(2 x 1) + (3 + 8)] assembly sequence, which may serve as reference for the syntheses of other sterically hindered long-chain glycans. 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 DD-heptoglycan and Ley tetrasaccharide. Glycan microarrays analysis of sera from rabbits immunized with isolated serotype O6 LPS revealed a humoral immune response to the α-(1→3)-linked heptoglycan, which is the key motif for designing glycoconjugate vaccines for H. pylori serotype O6.
