| Project/Area Number |
12556017
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | OSAKA CITY UNIVERSITY |
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Principal Investigator |
TNIGUCHI Makoto GRADUATE SCHOOL OF SCIENCE, OSAKA CITY UNIVERSITY PROFESSOR, 理学研究科, 教授 (00047309)
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| Co-Investigator(Kenkyū-buntansha) |
USUKI Yoshinosuke GRADUATE SCHOOL OF SCIENCE, OSAKA CITY UNIVERSITY LECTURER, 大学院・理学研究科, 講師 (30244651)
HIROTSU Ken GRADUATE SCHOOL OF SCIENCE,OSAKA CITY UNIVERSITY PROFESSOR, 理学研究科, 教授 (10047269)
TANAKA Toshio GRADUATE SCHOOL OF SCIENCE, OSAKA CITY UNIVERSITY ASSOCIATE PROFESSOR, 理学研究科, 教授 (10137185)
SAKANAKA Osamu MEIJI SEIKA KAISHA Co. Ltd., CHIEF RESEARCHER PHARMACEUTICAL TECHNOLOGY LABORATORY, 薬品技術研究所, 主任研究員
UEKI Masashi RIKEN INSTITUTE, ANTIBIOTICS LABORATORY, OSAKA CITY UNIVERSITY RESEARCHER, 抗生物質研究室, 研究員 (90312264)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2000: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | antifungal activity / respiratory inhibition / structure-activity relationship / 9-membered dilactone |
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| Research Abstract |
The effect of a novel antifungal agent, UK-2A, was found to be specific to fungal cells, not to any animal cells. Different from UK-2A, antimycin A, a structural analogue of UK-2A, showed effect on both cells and also induced the generation of reactive oxygen species. Although both compounds inhibited the electron transport at complex III in mitochondrion from various kinds of organisms, their effects on the reduction of cytochrome bc_1 complex in submitochondrial particles from bovine heart differ. This difference could cause their different effects on the generation of reactive oxygen species, accounting for the mechanism of the low cytotoxcity of UK-2A, which is its most prominent effect characteristic.
UK-2A could be used as agricultural chemicals. At present, the practical problems with this are the relatively low productivity and the poor durability of the antifungal activity.
As to the former problem, a polysaccharide produced by a certain filamentous fungus promoted the secretion of UK-2A outside the mycelia of UK-2A producing Actinomycete strain. This polysaccharide is a high molecular weight glucan having more than 50% of β-1, 3 bond at least.
As to the latter problem, an interesting fact from the study on structure-activity relationship was found. In this study, several compounds were synthesized by combining the structural features of UK-2A and Antimycin A. For example, A hybrid molecule, which was synthesized with the 9-memebered dilactone residue of UK-2A and the 3-formylaminosalicylic moiety of Antimycin A, showed the respiratory inhibition as much as UK-2A or Antimycin A, and demonstrated almost same extent of low cytotoxicity as UK-2A. Studies on the application of these compounds for agricultural chemicals are under progress.
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