Synthesis of endotoxic principle of bacterial lipopolysaccharide and its recognition by the innate immune systems of hosts.
A new stage of endotoxin research was brought about by structure elucidation and chemical synthesis of lipid A, the lipophilic partial structure of the lipopolysaccharide (LPS) of Gram-negative bacteria. Synthetic lipid A exhibited full endotoxic activity, which gave unequivocal evidence for the concept that lipid A is the active entity of endotoxin. Various lipid A analogues, as well as their radiolabeled derivatives and more complex partial structures of LPS, were also synthesized. By the use of these synthetic homogeneous preparations, not only simple studies on structure-activity relationships but precise and detailed analyses became possible on how this typical bacterial component is recognized by the innate immune receptor complex of mammalian cells.
Kusumoto
Shoichi
S
Suntory Institute for Bioorganic Research, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan. skus@sunbor.or.jp
Fukase
Koichi
K
D000818:Animals; D002478:Cells, Cultured; D006090:Gram-Negative Bacteria; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D008050:Lipid A / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D051218:Lymphocyte Antigen 96 / Q000276:immunology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D051197:Toll-Like Receptor 4 / Q000276:immunology
D008050:Lipid A; D051218:Lymphocyte Antigen 96; D051197:Toll-Like Receptor 4