Further study of biological activities of chemically synthesized analogues of lipid A in artificial membrane vesicles

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Abstract
Previously, chemically synthesized lipid A [a component of bacterial lipopolysaccharide] analogs such as the 1-monophosphate or 1,4''-diphosphate of 6-O-(2-deoxy-2-tetradecanoylamino-6-O-tetradecanoyl-D-glucopyranosyl)-2-deoxy-2-tetradecanoylamino-3,4-di-O-tetradecanoyl-D-glucopyranose enhanced immunogenicity of liposomal model membranes sensitized with amphipathic antigen when they were incorporated in the same liposomes. Here, this observation was extended by testing the recently synthesized analogs including diglucosamine analogs carrying hydroxy and acyloxy fatty acids. Among the analogs tested, those which showed higher adjuvant and mitogenic activities [in mice] in the liposomal system were N-acylated and O-acylated .beta.-1,6-linked D-glucosamine disaccharides carrying amide-bound 3-hydroxytetradecanoic acids in addition to PO43- in position 1 of the reducing sugar or amide-bound 3-tetradecanoyloxytetradecanoic acids. The analog carrying amide-bound 3-hydroxytetradecanoic acids and PO43- in position 4 of the non-reducing sugar showed weak adjuvant activity and marginal mitogenic activity.