title: Synthesis and immunomodulatory activities of Helicobacter pylori lipophilic terminus of lipopolysaccharide including lipid A.
abstract: Helicobacter pylori, a Gram-negative bacterium, causes gastroduodenal inflammatory diseases such as chronic gastritis and peptic ulcers, and is also a risk factor for gastric carcinogenesis. In this article, we review recent developments and findings in the chemical synthesis and immunomodulatory activities of H. pylori lipid A and 3-deoxy-D-manno-2-octulosonic acid (Kdo)-lipid A, to clarify the structural basis for the inflammatory response to H. pylori LPS. The synthetic methods include a new divergent synthetic approach with a widely applicable key intermediate for other types of lipid A structures, as well as a selective α-glycosylation reaction between Kdo and lipid A. Cytokine induction assays of the chemically synthesized lipid A structures showed selective cytokine induction depending on the patterns of acyl groups and phosphate groups. The results of cytokine induction assay suggested that H. pylori LPS can modulate the immune response during infection, and also plays a role in chronic inflammatory responses.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama Toyonaka, Osaka 560-0043, Japan. yukarif@chem.sci.osaka-u.ac.jp
authors.forename: Yukari
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimoyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suda
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
mesh_terms: D001681:Biological Assay; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D006031:Glycosylation; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000737:chemistry / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008050:Lipid A / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology; D008832:Microchemistry; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013400:Sugar Acids / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D008050:Lipid A; D013400:Sugar Acids; C120356:3-deoxy-manno-oct-2-ulopyranosonic acid