Adjuvant Action of Lipopolysaccharides and Derivatives. New Aspects of the Adjuvant Action of Lipid A and Its Analogs. Conference held in Airlie, Virginia on April 6 - 9, 1991

A typical lipid A (Escherichia coli type) is composed of glucosamine disaccharide backbone with 1,4'-bisphosphate and hexaacyl substituents at the 2, 2', 3 and 3' positions. We have synthesized lipid A analogs with monosaccharide backbone carrying phosphate and acyl substituents, and their biological activities examined. Analogs possessing monophosphate and triacyl substituents to monoglucosamine backbone were generally active. A representative analog (GLA- 60), which exhibits various immunomodulating activities such as induction of mediators, activation of B cells or macrophages, enhancement of nonspecific resistance and so on, has a 3-hydroxytetradeconoyl (C14-OH), a 3- tetradecanoyloxytetradecanoyl (C14-O-(C14)) and a phosphate groups at the 2, 3 and 4 positions of a glucosamine backbone, respectively. Tolerance inducing activity against lethal toxicity of LPS was, however, observed even in such scarcely active analogs.