1993 Fiscal Year Final Research Report Summary
STUDY ON THE MICROBIAL METABOLITRES AS THE MEDICINAL RESOURCES
| Project/Area Number |
03303013
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
IWASAKI Shigeo INST.MOL.CELL.BIOSCI., UNIV.KYOTO ; PROFESSOR, 分子細胞生物学研究所, 教授 (00013326)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 良博 共立薬科大学, 教授 (20050726)
YAMAZAKI Mikio FACUL.PHARM.SCI., UNIV.CHIBA ; PROFESSOR, 薬学部, 教授 (70089598)
NOZOE Shigeo FACUL.PHARM.SCI., UNIV.TOHOKU ; PROFESSOR, 薬学部, 教授 (50013305)
FUJITA Tetsuro FACUL.PHARM.SCI., UNIV.KYOTO ; PROFESSOR, 薬学部, 教授 (40027024)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Medicinal Resources / Microbial Products / Bioactivity / Natural Sources / Synthetic Supply |
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| Research Abstract |
This co-operative research project was organized to explore medicinal resources from the metabolites of microorganisms which are the producers of unlimitted numbers of novel bioactive compounds. In the research therm, the following results have been accumulated.
The microbial procducts that interfere with microtubule functions have been searched and ustiloxins were isolated. Their interaction with tubulin have been clarified (IWASAKI). A generic cynthetic method for peptibols, TS-Bs, was established. A ion channel formation mechanism by peptibols in biomembranes and lipid bilayrs was deduced (FUJITA). Several new compounds having antitumor activity and the activities towards glutamate receptor have been isolated from mashroom extracts. Their chemical structures were determined and the structure-activity relationships were examined (NOZOE). Fifteen new monoamine oxidase (MAO)-inhibitory compounds were isolated from the metabolites of Ascomycetes. Their structures and structure-activity relationships were studied (YAMAZAKI). Microtubule disruption by synthetic and natural estrogens were proved by Chinese hamster V79 cells in culture, and were correlated with their cytotoxicity and growth inhibitory activity (SATO). The neurogenesis inducer, lactacystin, and the gp120-CD4 binding inhibitors, isochromophilones I, II and WK-3419B were discovered (TANAKA). Biosynthetic pathway of lactacystin and its stereochemical aspect were investigated by feeding experiments of radio-labeled precursors (NAKAGAWA). Polyol segment of pentamycin was synthesized stereoselectively based on a convergent synthesis of 1,3-polyol. Synthesis of right half of mycalamide A was accomplished, which constututes a formal total synthesis of mycalamide As a total assymmetric synthesis of ISP-I, an immunosuppressive component from Isalia sinclairii, constructuion of the synthetic fragments A,B,C and connection of these fragments were succesfully achieved.
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