ENZYMATIC-SYNTHESIS OF ANALOGS OF BACTERIAL LIPID-A AND DESIGN OF BIOLOGICALLY-ACTIVE LPS-ANTAGONISTS AND LPS-MIMETICS

Lipid A, the lipid anchor of lipopolysaccharide (LPS) to the outer mem brane of Gram-negative bacteria may be regarded as the most potent imm unostimulatory but highly endotoxic substance. In a search for clinica lly useful substructures of lipid A, we synthesized analogs of lipid X , the reducing monosaccharide of lipid A, and of UDP-Lipid X as potent ial substrates for bacterial lipid A synthase, and obtained acylated g lucosamine-(1-->6)-disaccharide-1-phosphates in good yield. The LPS-mi metic monosaccharide SDZ MRL 953 appears to represent the minimum subs tructure of lipid A with immuno-stimulatory properties of potential cl inical relevance.