title: Biological activities of chemically synthesized partial structure analogues of lipid A.
abstract: Analogues of the nonreducing sugar part of lipid A were chemically synthesized and tested for biological activities such as Limulus amebocyte lysate gelation, interferon- and tumor necrosis factor-induction, lethal toxicity in galactosamine-sensitized mice, and pyrogenicity. A 4-O-monophosphorylglucosamine derivative possessing 2-N-3-tetradecanoyl-oxytetradecanoyl and 3-O-tetradecanoyl groups (GLA-27) exhibited all activities tested except for pyrogenicity. Alteration of the acyl substituents or dephosphorylation as well as acylation or phosphorylation of the 6-OH caused most activities of GLA-27 to diminish or disappear altogether. On the other hand, the biological activities expressed by GLA-27 were not significantly affected even when the glucosamine backbone was changed to 1-deoxy type, epimer type at C-3 (allose form), or 3-amino type. These results indicate that the acyl substituents and the phosphorylation positions rather than the backbone structures in these partial structure analogues of lipid A affect the expression of biological activities of endotoxin. The results also clearly indicate that some biological activities of endotoxin can be expressed separately from pyrogenicity.
mesh_terms: D000818:Animals; D005260:Female; D005688:Galactosamine / Q000633:toxicity; D006023:Glycoproteins / Q000096:biosynthesis; D007369:Interferon Inducers; D008033:Limulus Test; D008050:Lipid A / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D011425:Propionibacterium acnes / Q000378:metabolism; D011749:Pyrogens; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
chemical_list: D006023:Glycoproteins; D007369:Interferon Inducers; D008050:Lipid A; D011749:Pyrogens; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine