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 ...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.展开更多
Treponema is a Gram-negative anaerobic bacterium,among which the pathogenic Treponema can cause various diseases,such as venereal syphilis(Treponema pallidum),yaws(Treponema carateum),and oral diseases(Treponema denti...Treponema is a Gram-negative anaerobic bacterium,among which the pathogenic Treponema can cause various diseases,such as venereal syphilis(Treponema pallidum),yaws(Treponema carateum),and oral diseases(Treponema denticola and Treponema medium).Although different from conventional lipopolysaccharides,the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development.Hence,we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L-ornithine(L-Orn)and D-aspartic acid(D-Asp)derivatives.The efficiency of non-reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors.Our[3+1]glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group,thereby improving the efficiency of synthesizing the target tetrasaccharide.The L-Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency.Therefore,the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional-group modifications have provided valuable insights for synthesizing other complex bacterial glycans.展开更多
Carbohydrates play critical roles in mediating many biological processes, such as cell growth, migration, cell-cell adhesion, fertilization, signal transduction and immune response. The increasing demands for the stud...Carbohydrates play critical roles in mediating many biological processes, such as cell growth, migration, cell-cell adhesion, fertilization, signal transduction and immune response. The increasing demands for the study of these molecules greatly facilitate the development of carbohydrate synthesis. Inversion strategies via sulfonyl groups, selective reductions, etc. have been used to synthesize corresponding inverted configurations. This review focuses on the mechanisms of these inversion methods and their applications in constructing amino sugars, rare sugars and E-configurations in glycosylations.展开更多
基金financial support from the National Natural Science Foundation of China(22177041,22277042,22077052,22107037,22207042)the China Postdoctoral Science Foundation(2021M691279)+1 种基金the 111 Project(111-2-06)the Max Planck Society International Partner Group Program,and the China Scholarship Council(CSC)for funding.P.H.S.thanks the Max Plank Society forgenerous financial support.
文摘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.
基金the National Natural Science Foundation of China(22325803,22077052,22277042,22107037,22177041,22207042)the China Postdoctoral Science Foundation(2021M691279)the National Key R&D Program of China(2023YFC2308000).
文摘Treponema is a Gram-negative anaerobic bacterium,among which the pathogenic Treponema can cause various diseases,such as venereal syphilis(Treponema pallidum),yaws(Treponema carateum),and oral diseases(Treponema denticola and Treponema medium).Although different from conventional lipopolysaccharides,the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development.Hence,we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L-ornithine(L-Orn)and D-aspartic acid(D-Asp)derivatives.The efficiency of non-reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors.Our[3+1]glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group,thereby improving the efficiency of synthesizing the target tetrasaccharide.The L-Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency.Therefore,the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional-group modifications have provided valuable insights for synthesizing other complex bacterial glycans.
基金the National Natural Science Foundation of China(No. 21302068)the Natural Science Foundation of Jiangsu Province, China (No. BK20150140)+1 种基金the Fundamental Research Funds for the Central Universities(No. JUSRP51712B)the Public Health Research Center at Jiangnan University(No. JUPH201502)
文摘Carbohydrates play critical roles in mediating many biological processes, such as cell growth, migration, cell-cell adhesion, fertilization, signal transduction and immune response. The increasing demands for the study of these molecules greatly facilitate the development of carbohydrate synthesis. Inversion strategies via sulfonyl groups, selective reductions, etc. have been used to synthesize corresponding inverted configurations. This review focuses on the mechanisms of these inversion methods and their applications in constructing amino sugars, rare sugars and E-configurations in glycosylations.
