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The bacterium Vibrio vulnificus can cause severe infections internally and externally. The mortality rate of V. vulnificus -associated gangrene and septicemia has increased due to antibiotic resistance and the absence of human vaccine. Bacterial carbohydrates have been widely used in the development of bacterial vaccines. Here, a rare l -Gal p NAmA-containing disaccharide that exists in V. vulnificus biotype 2 serovar A O-antigen was synthesized from d -glucose and l -galactose. An investigation on the influence of different linkers on the disaccharide synthetic efficiency indicated that the amine linker has more practicality. Two α-glycosidic linkages were constructed with good stereoselectivity by using nonparticipating C2 azido group and solvent effect. An orthogonal protection strategy allowed introductions of carboxyl and acetamidino (Am) groups at the disaccharide stage. The synthesis of the amine-linked disaccharide will provide a basis for the preparation of the trisaccharide repeating unit and longer fragments of V. vulnificus biotype 2 serovar A O-antigen, as well as other complex glycans. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Helicobacter pylori (H. pylori) infection is a threat to human health. The lipopolysaccharide (LPS) O‐antigen holds promise for developing vaccines. It is meaningful to explore the immunological activity of oligosaccharides with different lengths and frameshifts for antigen development. Herein, a glycan library of H. pylori O2 O‐antigen containing eight fragments is constructed. After screening with anti‐H. pylori O2 LPS sera and patients' sera by glycan microarray, the disaccharide HPO2G‐2b and trisaccharide HPO2G‐3a show strong antigenicity and then are separately conjugated with carrier protein CRM197. Both glycoconjugates elicit a robust immunoglobulin G (IgG) immune response in rabbits. The anti‐HPO2G‐3a IgG antibodies possess a much stronger binding affinity with the LPS and bacteria of H. pylori O2 than the anti‐HPO2G‐2b IgG antibodies. There is no cross‐reaction between both sera IgG antibodies with LPS and bacteria of H. pylori O1, O6, and E. coli. The results demonstrate the trisaccharide HPO2G‐3a is a promising candidate for H. pylori vaccine development. [ABSTRACT FROM AUTHOR]

Exploiting synergistic remote participation effects of acyl groups at the O3 and O6 positions was key to the complete α-selectivity during the total synthesis of the unique (1 → 2)- and (1 → 3)-linked α-oligoglucosides from the Helicobacter pylori O2 O-antigen. Acyl remote participation and solvent effects were found to counteract during α-stereoselective glucosylations for the first time. The resulting antigen is a lead for the development of a carbohydrate-conjugate vaccine. [ABSTRACT FROM AUTHOR]

AbstractHelicobacter 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. [ABSTRACT FROM AUTHOR]

Abstract: Helicobacter pylori, a widespread gastric bacterial pathogen that infects 90 % of the population in developing countries, causes chronic gastritis, peptic ulcers and gastric cancer. Battling H. pylori infection is a serious challenge due to the increased resistance to antibiotics and the lack of vaccines. The lipopolysaccharide covering the H. pylori cell‐surface outer membrane is an attractive target for the development of a glycoconjugate vaccine. Here, we report a [3+5] convergent synthesis of an outer core octasaccharide of H. pylori employing just three orthogonally protected building blocks. A synergistic glycosylation strategy enables the creation of five pivotal 1,2‐cis‐α‐glucosidic bonds consist of four types of linkages using just three monomers. This strategy can be expanded to many 1,2‐cis‐α‐gluoside‐containing oligosaccharides both in solution and solid phase. [ABSTRACT FROM AUTHOR]

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., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Helicobacter pylori, a widespread gastric bacterial pathogen that infects 90 % of the population in developing countries, causes chronic gastritis, peptic ulcers and gastric cancer. Battling H. pylori infection is a serious challenge due to the increased resistance to antibiotics and the lack of vaccines. The lipopolysaccharide covering the H. pylori cell-surface outer membrane is an attractive target for the development of a glycoconjugate vaccine. Here, we report a [3+5] convergent synthesis of an outer core octasaccharide of H. pylori employing just three orthogonally protected building blocks. A synergistic glycosylation strategy enables the creation of five pivotal 1,2-cis-α-glucosidic bonds consist of four types of linkages using just three monomers. This strategy can be expanded to many 1,2-cis-α-gluoside-containing oligosaccharides both in solution and solid phase., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)