Chemical Synthesis and Immunological Evaluation of Helicobacter pylori Serotype O6 Tridecasaccharide O‐Antigen Containing a dd‐Heptoglycan. Issue 32 (27th May 2020)

• Record Type: Journal Article
• Authors: Tian, Guangzong; Hu, Jing; Qin, Chunjun; Li, Lingxin; Zou, Xiaopeng; Cai, Juntao; Seeberger, Peter H.; Yin, Jian
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 32(2020)
• Page Start: 13362
• Page End: 13370
• Publication Date: 2020-05-27
• Subjects: antigens -- immunology -- glycans -- oligosaccharides -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202004267
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 α‐(1→3)‐, α‐(1→6)‐, and α‐(1→2)‐linked heptoglycan, and a β‐d ‐galactose connector, by an [(2×1)+(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 α‐(1→3)‐linked heptoglycan, a key motif for designing glycoconjugate vaccines for H. pylori serotype O6. Abstract : Molecular decoy : The Helicobacter pylori serotype O6 tridecasaccharide O‐antigen containing a terminal Le y tetrasaccharide and a unique dd ‐heptoglycan was chemically synthesized for the first time. Immunological investigation based on seven synthetic oligosaccharides revealed that the α‐(1→3)‐linked dd ‐heptoglycan is a key motif for designing glycoconjugate vaccines against H. pylori, while the Le y tetrasaccharide may serve as a decoy to the immune system.