The 2-aminogluconate isomer of rhizobium sin-1 lipid A can antagonize TNF-alpha production induced by enteric LPS |
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Authors: | Lee Hyi-Seung Wolfert Margreet A Zhang Yanghui Boons Geert-Jan |
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Affiliation: | Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA. |
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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. |
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Keywords: | antagonists lipids lipopolysaccharides septic shock tumor necrosis factor |
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