抄録
Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria, and known as endotoxin for its potent immunostimulating and inflammatory activities. Lipid A is the active principal of LPS and links to the polysaccharide via the peculiar acidic sugar, Kdo. LPS of Helicobacter pylori and Porphyromonas gingvalis show much lower inflammatory activity than other enterobacterial LPS such as Escherichia coli. Recent studies suggested that the H. pylori and P gingvalis LPS are associated with chronic inflammation and atherosclerosis. We have thus synthesized the H. pylori and P gingvalis LPS partial structures to elucidate their biological functions. In comparison with E. coli lipid A, lipid As of H. pylori and P gingvalis have the distinctive several chemical structures. In order to synthesize various lipid A structures, which include H. ylori and P gingivalis lipid As, we developed a strategy for the comprehensive synthesis using an appropriately protected disaccharide backbone as a common key intermediate. We also improved the a-selective glycosylation method between Kdo and lipid A backbone. The immunological activities of the synthesized structures were then observed. H. pylori lipid A with 1-phosphate la showed inhibitory activity against IL-6 induction of E. coli LPS, whereas lipid A with aminoethanol phosphate lb showed weak IL-6 inducing activity. On the other hand, both la and lb induced IL-18, which has been shown to correlate with chronic inflammation. The results suggested that the biological activities of the parasitic bacterial LPS strongly correlate to the pathogenicity of the bacteria, by selective inhibition or activation of different pathways depending on the subtle differences in their structures.
