Biological activities of chemically synthesized N-acetylneuraminic acid-(alpha 2----6)-monosaccharide analogs of lipid A.
The mitogenicity and lethal toxicity of chemically synthesized lipid A analogs, in which 2,3-acyloxyacylglucosamine-4-phosphate linked to tetraacetyl-N-acetylneuraminic acid (compound A-207) or to N-acetylneuraminic acid (compound A-307), were examined. Although the mitogenic activity of the synthetic compounds was weaker than that of bacterial LPS, doses of 10-50 micrograms/ml of A-207 and 5-10 micrograms/ml of A-307 were capable of increasing incorporation of [3H]thymidine into cultured spleen cells of C57BL/6 mice. Lethal toxicity of A-207 was observed at 10 micrograms/mouse in C57BL/6 mice sensitized with D-galactosamine hydrochloride. However, the attachment of tetraacetyl-N-acetylneuraminic acid or N-acetylneuraminic acid does not appear to enhance the biological activity of acyloxyacylglucosamine-4-phosphate.
Shimizu
T
T
Department of Microbiology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Masuzawa
T
T
Yanagihara
Y
Y
Shimizu
C
C
Ikeda
K
K
Achiwa
K
K
D000818:Animals; D002478:Cells, Cultured; D005944:Glucosamine / Q000031:analogs & derivatives / Q000633:toxicity; D007928:Lethal Dose 50; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000138:chemical synthesis; D019158:N-Acetylneuraminic Acid; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development; D012794:Sialic Acids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism
D008050:Lipid A; D008934:Mitogens; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid; D005944:Glucosamine