The 2-Aminogluconate Isomer of Rhizobium sin-1 Lipid A Can Antagonize TNF-α Production Induced by Enteric LPS
✍ Scribed by Hyi-Seung Lee; Margreet A. Wolfert; Yanghui Zhang; Geert-Jan Boons
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 178 KB
- Volume
- 7
- Category
- Article
- ISSN
- 1439-4227
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✦ Synopsis
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‐α 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‐__α protein production. This compound was, however, able to antagonize the production of TNF‐α induced by enteric LPS; this indicates that the 2‐aminogluconate form of R. sin‐1 lipid A is responsible for its biological properties.