Antigenicity evaluation of synthetic α-(1,3)-linked D, D-heptoglycan of Helicobacter pylori serotype O6 lipopolysaccharide

Abstract

Helicobacter pylori, a gram‐negative bacterium, is known to be associated with various gastric pathologies including chronic gastritis, peptic ulcers and gastric carcinoma. Despite the emerging issue of bacterial resistance to antibiotic-based combination therapy, there is currently no vaccine available for H. pylori infection in the market. Here, we report the synthesis of α-(1,3)-D,D-heptoglycan with different chain length from the lipopolysaccharide of H. pylori serogroup O6. The [n + 1] iterative glycosylation strategy was used for heptoglycan chain elongation. The trifluoroacetimidate heptoside donor exhibited much higher efficiency than thioglycoside donor during glycosylation. An antigenicity evaluation using glycan microarrays indicated that α-(1,3)-D,D-hepto-disaccharide, pentasaccharide and hexasaccharide showed stronger binding affinity to IgG antibodies of H. pylori O6 LPS immunized rabbit serum or serum of H. pylori infected patients. These findings provide significant structure − activity relationship information for developing carbohydrate-based vaccines against H. pylori containing α-(1,3)-D,D-heptoglycan.

GRAPHICAL ABSTRACT

Keywords:

• Helicobacter pylori
• α-(1,3)-D,D-heptoglycan
• chemical synthesis
• glycosylation
• glycan microarrays

Disclosure statement

The authors declare no competing financial interests.

Supplemental material

NMR spectra for all pure products, figure of rabbit sera glycan microarray slides and figure of patient sera glycan microarray slides. This material is available free of charge via the Internet.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant Numbers 22325803, 22077052, 22277042, 22177041, 22207042, 22107037; Open Project of Key Laboratory of Carbohydrate Chemistry and Biotechnology (Jiangnan University), Ministry of Education under Grant Number KLCCB-KF202203.