| Project/Area Number |
09306014
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Fisheries chemistry
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
FUSETANI Nobuhiro GRAD.SCH.AGRIC.LIFE SCI., THE UNIVERSITY OF TOKYO PROFESSOR, 大学院・農学生命科学研究科, 教授 (70012010)
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| Co-Investigator(Kenkyū-buntansha) |
WATABE Shugo GRAD.SCH.AGRIC.LIFE SCI., THE UNIVERSITY OF TOKYO PROFESSOR, 大学院・農学生命科学研究科, 教授 (40111489)
IKEGAMI Susumu HIROSHIMA UNIV.FAC.APPL.BIOSCI.PROFESSOR, 生物生産学部, 教授 (80011980)
KARAKI Hideaki GRAD.SCH.AGRIC.LIFE SCI., THE UNIVERSITY OF TOKYO PROFESSOR, 大学院・農学生命科学研究科, 教授 (60011912)
MATSUNAGA Shigeki GRAD.SCH.AGRIC.LIFE SCI.THE UNIVERSITY OF TOKYO ASSOCIATE PROFESSOR, 大学院・農学生命科学研究科, 助教授 (60183951)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥26,200,000 (Direct Cost: ¥26,200,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1997: ¥10,300,000 (Direct Cost: ¥10,300,000)
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| Keywords | marine sponge / bioactive compound / actin / alkaloid / calmodulin / echinoderm embryo / enzyme inhibitor / macrolide / 水圏無脊椎動物 / ホヤ / 細胞毒性 / 平滑筋 / ヒトデ胚 / リン酸化 / 酵素阻害 / 酵素阻止 / ペプチド / カリクリン / 動物細胞 / 水圈無脊椎動物 / アクチン脱重合 / 孵化酵素 / マイカロライド / 海洋天然物質 / タンパク質脱リン酸化酵素 / カソクリン |
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| Research Abstract |
A number of marine invertebrates including sponges, soft corals, and tunicates collected from various Japanese coasts has been tested for cytotoxicity against P388 leukemia cells, morphological changes-inducing activity in rat neuroblast 3Y1, inhititory activity against serine proteases, cystein proteases, metalloproteinases, and glycosidases. Isolation and structure elucidation of active constituents from promising specimens resulted in discovery of 71 new compounds, among which calmodulin-inhibiting alkaloids were included. Biological activity studies of new calyculin derivatives and those derived chemically from calyculin A led to important insights into the interaction of calyculins with protein phosphatases.
Detailed analyses of modes of action of selective compounds obtained led to several inportant findings. Mycalolides/kabiramides bind to a different site of actin from those of cytochalasin D and latrunculin A.Bistheonellide A bind to G-actin in a molar ration of 1 : 2 to inhibit actin polymerization. Stellettamide A and related alkaloids induce contraction of smooth muscles which was found to be due to inhibition of phosphorylation of myosin light chain by inhibiting calmodulin. It was also found that discodermin A forms pores in biomembranes and that theonellamides A and F interact with dehydrogenases.
In search for metabolites affecting development of echinoderm embryos, several active substances were isolated from sponges including ancorinoside A and rhopaloic acids. Jaspisin was found to inhibit selectively a hatching enzyme of sea urchin, a matrix endopeptidase. Finally, a simple system to detect inhibitors of protein phosphatases such as okadaic acid and calyculin A by using antibodies which differentiate specific phosphorylated amino acids in ANO39, an endoplasmic reticulum protein of sea urchin eggs.
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