2017 Fiscal Year Final Research Report
Basic pharmaceutical study of relationship between phosphorus atom introduction and non-competition of inhibitor
| Project/Area Number |
15K08033
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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 | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊集院 良祐 東京薬科大学, 薬学部, 助教 (40442925)
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| Project Period (FY) |
2015-10-21 – 2018-03-31
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| Keywords | セリンプロテアーゼ阻害剤 / ホスホネート / 非競合阻害剤 / トロンビン |
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| Outline of Final Research Achievements |
We conducted basic research aiming at elucidating the inhibitory molecular mechanism of phosphonate compounds which show inhibitory activity only to thrombin among serine proteases, and also bind to sites different from the substrate binding site to show inhibitory activity. The conversion of the phosphonate site of the present compound to the carboxylate show competitive type inhibition and the enzyme selectivity decreases. This phenomena is a very interesting because the inhibition mode shows quite different only converted carbonyl group to phosphoryl group. However, the present compounds since strength and enzyme selectivity of the activity was not sufficient, in the present study were subjected to structural development was oriented to improve the activity and selectivity. As a result, various valuable information to increase the inhibition ability and enzyme selectivity was obtained.
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| Free Research Field |
創薬化学
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