| Project/Area Number |
01850199
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
高分子合成
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| Research Institution | University of Tokyo |
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Principal Investigator |
URYU Toshiyuki University of Tokyo, Institute of Industrial Science, Professor, 生産技術研究所, 教授 (80011005)
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| 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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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1990: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1989: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | AIDS-virus drug / Curdlan sulfate / Lentinan sulfate / AIDS drug / L-Glucose-branched ribofuranan / Sulfated polysaccharide / Anti-HIV activity / Low anticoagulant activity / カ-ドラン硫酸 / リボフラナン硫酸(RS) / マンノピラナン硫酸(MS) / 抗凝血活性 / 硫酸化アルキルオリゴ糖 / 硫酸化L糖分枝多糖 / 生分解性 / カ-ドラン / レンチナン / Lーグルコ-ス分枝カ-ドラン硫酸 / Dーグルコ-ス分枝カ-ドラン硫酸 / 抗エイズウイルス作用 / 抗原陽性率 / 全アセチル化カ-ドラン / 部分アセチル化カ-ドラン / Lーグルコ-ス |
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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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