2014 Fiscal Year Final Research Report
SBDD targeting metalloenzyme RNA polymeraze of influenza virus
| Project/Area Number |
24590141
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | University of Shizuoka |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Hideshi 静岡県立大学, 薬学部, 講師 (70433208)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | インフルエンザ / 阻害剤 / 金属酵素 / ジケト酸 / RNAポリメラーゼ / SBDD / ドッキング / 結晶構造 |
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| Outline of Final Research Achievements |
We planed structure-based drug design of new diketo acid derivatives targeting the subunit PAN of RNA polymerase of influenza virus and inhibiting the metalloenzyme by chelation. The phenyl and biphenyl diketo acids with a nitro or carboxy group as hydrogen bond acceptor were synthesized. Of these, a biphenyl diketo acid with a carboxy group showed the most potent inhibitory effect against the nuclease activity of PAN. A good correlation between the inhibitory activity of the diketo acids with a carboxy group and their docking energies was shown. In addition, single crystals of PAN were obtained, and the X-ray crystallographic analysis was successfully done.
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| Free Research Field |
創薬化学
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