2-aminogluconate isomer of Rhizobium sin-1 lipid A can antagonize TNF-a production induced by enteric LPS

Abstract

The naturally occurring LPS from Rhizobium sin-1 can prevent the induction of TNF-α induced by enteric LPS. The proximal saccharide moiety of R. sin-1 lipid A can exist in two forms 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, a new derivative, which contains a methyl ether at the C-5 hydroxyl was prepared by a highly convergent approach using a key disaccharide building block and its inflammatory properties studied. 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, indicating that the 2-aminogluconate form of R. sin-1 lipid A is responsible for its biological properties.