| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Takashi University of Tokyo, Institute of Industrial Science, Research Associate, 生産技術研究所, 助手 (40166955)
HATANAKA Kenichi Tokyo Institute of Technology, Faculty of Life Science and Engineering, Associat, 生命理工学部, 助教授 (70167584)
YAMAMOTO Naoki Tokyo Medical and Dental University, School of Medicine, Professor, 医学部, 教授 (00094053)
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| Research Abstract |
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.
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