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.
D000818:Animals; D005260:Female; D005944:Glucosamine / Q000031:analogs & derivatives; D006023:Glycoproteins / Q000096:biosynthesis; D007369:Interferon Inducers; D008033:Limulus Test; D008050:Lipid A; D051379:Mice; D011749:Pyrogens; D011817:Rabbits; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D007369:Interferon Inducers; D008050:Lipid A; D011749:Pyrogens; D014409:Tumor Necrosis Factor-alpha; D005944:Glucosamine