Biological Activities of Chemically Synthesized Analogues of the Nonreducing Sugar Moiety of Lipid A

Biological activities of five synthetic lipid A analogues (D-glucosamine derivatives) were examined to elucidate the structure required for expression of the biological activities of endotoxin. Proclotting enzyme of horseshoe crab activation, interferon-inducing and tumor necrosis factor-inducing activities were significantly expressed by an analogue which possesses 4-O-phosphoryl, 3-O-tetradecanoyl and N-tetradecanoyloxytetradecanoyl groups. The results obtained with different analogues show that the 4-O-phosphoryl and N-tetradecanoyloxytetradecanoyl groups are important for expression of the above activities. The effect of 6-O-acylation in preventing the expression of these biological activities is also suggested. Pyrogenic activity was not detected in any of the compounds tested.