Synthesis of lipid A monosaccharide analogues containing acidic amino acid: exploring the structural basis for the endotoxic and antagonistic activities.
For elucidation of the structural and conformational requirements on the endotoxic and antagonistic activity of lipid A derivatives, we designed and synthesized lipid A analogues containing acidic amino acid residues in place of the non-reducing end phosphorylated glucosamine. Definite switching of the endotoxic or antagonistic activity was observed depending on the difference of the acidic groups (phosphoric acid or carboxylic acid) in the lipid A analogues.
Akamatsu
Masao
M
Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
Fujimoto
Yukari
Y
Kataoka
Mikayo
M
Suda
Yasuo
Y
Kusumoto
Shoichi
S
Fukase
Koichi
K
D000215:Acylation; D024342:Amino Acids, Acidic / Q000737:chemistry* / Q000633:toxicity; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis; D008033:Limulus Test; D008050:Lipid A / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
D024342:Amino Acids, Acidic; D004731:Endotoxins; D015850:Interleukin-6; D008050:Lipid A; D008070:Lipopolysaccharides