Synthesis of Polymeric AIDS Dryg with Lasting Activity

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Such synthetic polysaccharides as ribofuranan, xylofuranan, and dextran sulfates showed not only high anti-AIDS virus (anti-HIV) activity, but also high anticoagulant activity which is assumed to be side effects. In this study, sulfated polysaccharides with high anti-HIV activity but low anticoagulant activity were for the first time synthesized. A 1, 3-beta-linked antitumor polysaccharide lentinan was sulfated with piperidine N-sulfonic acid to afford lentinan sulfate. Lentinan sulfate had high anti-HIV activity inhibiting completely AIDS virus infection to T lymphocytes in a concentration as low as 3.3 mug/ml in vitro. Moreover, it showed low anticoagulant activity of about 20 unit/mg. Next, a bacterial polysaccharide curdlan having the same backbone structure as lentinan was sulfated by the same method to give curdlan sulfate. Curdlan sulfate had a high anti-HIV activity which inhibits the virus infection in a a 3.3 mug/ml concentration, and showed low anticoagulant activity of 15 unit/mg. The curdlan sulfate introduced into animal blood was transported into such tissues as liver, kidney, lymph node, and bone marrow, disappearing from the blood in 60-180 minutes after injection. To keep the concentration of curdlan sulfate in blood in a high level for longer time, such nonnatural sugars as L-glucose and L-mannose were reacted with curdlan and syntheric ribofuranan to form L-glycosyl branchings. For L-glyscosyl-branched polysaccharide sulfates, in vivo retention time of the anticoagulant activity in blood was a few hours. It was revealed that the absorbed curdlan sulfate exisis in the tissue for a few ten days without being subjected to main chain degradation. Syntheric 1, 6-alpha-D-mannan sulfate had high anti-HIV activity and medium anticoagulant activity.