Chemical Structure and Biologic Activity of Bacterial and Synthetic Lipid A

• Published in: Reviews of infectious diseases 1987-09, Vol.9, p.S527-S536
• Main Authors: Ernst T. Rietschel, Brade, Lore, Klaus Brandenburg, Hans-Dieter Flad, Jacqueline de Jong-Leuveninck, Kazuyoshi Kawahara, Buko Lindner, Harald Loppnow, Thomas Lüderitz, Ulrich Schade, Ulrich Seydel, Zygmunt Sidorczyk, Angelika Tacken, Zähringer, Ulrich, Brade, Helmut
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Chemical Phenomena; Chemistry; Disaccharides; Endotoxins; Escherichia coli; Fatty acids; Gram-Negative Bacteria; Hydroxyls; Lipid A - analysis; Lipid A - chemical synthesis; Lipid A - immunology; Lipid A - toxicity; Lipids; Lipopolysaccharides; Molecular structure; Salmonella
• ISSN: 0162-0886

The chemical structure of the lipid A component of enterobacterial lipopolysaccharide (LPS) is now known in some detail. For example, lipid A of Escherichia coli consists of a β(1→6)-linked D-glucosamine disaccharide that carries four (R)-3-hydroxytetradecanoyl groups in positions 2, 3, 2', and 3' and two phosphoryl residues in positions 1 and 4'. The hydroxy fatty acids at positions 2' and 3' are acylated at their 3-hydroxyl groups by dodecanoic acid and tetradecanoic acid, respectively. The hydroxyl groups in positions 4 and 6' are free, the latter serving as the attachment site for the polysaccharide component in intact LPS. On the basis of this structure, E. coli-type lipid A and partial structures thereof have been chemically synthesized (group of T. Shiba, Osaka University, Osaka, Japan) and analyzed for endotoxic activity. In all in vivo and in vitro test systems employed (including lethal toxicity, pyrogenicity, local Shwartzman reactivity, B lymphocyte mitogenicity, macrophage activation, and serologic cross-reactivity with lipid A antiserum), synthetic lipid A has activity identical to that of E. coli lipid A. These findings support the structural proposal for lipid A and prove the previous hypothesis that the endotoxic principle is embedded in lipid A.