Synthesis of lipid A monosaccharide analogues containing acidic amino acid: Exploring the structural basis for the endotoxic and antagonistic activities

For elucidation of the structural and conformational requirements on the endotoxic and antagonistic activity of lipid A derivatives, we designed and synthesized lipid A analogues containing acidic amino acid residues in place of the non-reducing end phosphorylated glucosamine. Definite switching of the endotoxic or antagonistic activity was observed depending on the difference of the acidic groups (phosphoric acid or carboxylic acid) in the lipid A analogues.

Lipid A monosaccharide analogues possessing acidic amino acid were synthesized. Aspartic acid-substituted analogues exhibited endotoxicity, and in contrast phosphoserine-substituted ones behaved as antagonists.Figure optionsDownload as PowerPoint slide