Lipid A monosaccharide analogues inhibiting oxidative phosphorylation.

Three acyl-glucosamine analogues of "lipid A" and an acyl-glucose analogue of "cord factor" were synthesized and their activity was tested on isolated rat liver mitochondria. The 4 glycolipids slightly inhibited succinate-supported active respiration and strongly inhibited glutamate-supported active respiration. The most potent inhibitors were the two diacylated compounds which are the most hydrophobic. Phosphorylation was also impaired. Comparison of our results with the few published data about the effects of lipid A on mitochondria indicated that the two diacylated glucosamines were as active as their natural model. The minimal requirements to obtain a glycolipid structure with an activity resembling that of lipid A is discussed.