title: The 2-aminogluconate isomer of rhizobium sin-1 lipid A can antagonize TNF-alpha production induced by enteric LPS.
abstract: The naturally occurring lipopolysaccharide (LPS) from Rhizobium sin-1, a nitrogen-fixing bacterial species, can prevent the induction of the tumor necrosis factor TNF-alpha induced by enteric LPS. The proximal saccharide moiety of R. sin-1 lipid A can exist in two forms, namely as a 2-aminogluconolactone or 2-aminogluconate. As it is unknown which of these forms is responsible for the antagonistic properties of R. sin-1 lipid A, compound 4 was prepared, and its inflammatory properties were studied. This compound contains a methyl ether at the C-5 hydroxyl, which prevents lactonization and therefore is ideally suited to determine whether the 2-aminogluconate possesses antagonistic properties. Compound 4 was synthesized by a highly convergent approach with a key disaccharide building block functionalized with a set of orthogonal protecting groups. The novel synthetic compound lacks proinflammatory properties, as indicated by an absence of TNF-alpha protein production. This compound was, however, able to antagonize the production of TNF-alpha induced by enteric LPS; this indicates that the 2-aminogluconate form of R. sin-1 lipid A is responsible for its biological properties.
authors.affiliation: Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
authors.forename: Hyi-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Margreet A
authors.initials: MA
authors.lastname: Wolfert
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D005942:Gluconates / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007536:Isomerism; D008050:Lipid A / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012231:Rhizobium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D005942:Gluconates; D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha