title: Predominant role of the substituents on the hydroxyl groups of 3-hydroxy fatty acids of non-reducing glucosamine in lipid A for the endotoxic and antagonistic activity.
abstract: The synthetic disaccharide precursor of lipid A (406: identical to lipid IVA) was found to reduce its endotoxic activity in mice by an order of 10(5) or more, by replacing the hydroxyl groups with succinyl or acetyl residues. Both the succinylated and acetylated 406 were also found to antagonize the endotoxic mitogenicity on murine splenocytes. Previous studies demonstrated that the succinylated or acetylated synthetic complete lipid A preparations retained the whole endotoxic activity [1994, Infect. Immunol. 62, 1705]. The drastic contrast in all of these results suggests the importance of the substituents on the hydroxyl groups of 3-hydroxy fatty acids of non-reducing glucosamine of lipid A for the activity and for transformation to the antagonistic structure.
authors.affiliation: National Institute of Health Sciences, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanamoto
mesh_terms: D000107:Acetylation; D000818:Animals; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity; D005227:Fatty Acids / Q000737:chemistry*; D005260:Female; D005944:Glucosamine / Q000737:chemistry* / Q000633:toxicity; D017665:Hydroxyl Radical; D008050:Lipid A / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008938:Mitosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013386:Succinates / Q000737:chemistry; D019802:Succinic Acid
chemical_list: D004731:Endotoxins; D005227:Fatty Acids; D008050:Lipid A; D013386:Succinates; D017665:Hydroxyl Radical; D019802:Succinic Acid; D005944:Glucosamine