| Project/Area Number |
15K08034
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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 | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
丹羽 典朗 日本大学, 薬学部, 准教授 (20541973)
齋藤 弘明 日本大学, 薬学部, 講師 (30385976)
鈴木 守 大阪大学, たんぱく質研究所, 准教授 (40280507)
小林 弘子 日本大学, 薬学部, 准教授 (50216066)
高宮 知子 日本大学, 薬学部, 講師 (50513917)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | カテコールO-メチル転移酵素 / 生成物阻害 / S-アデノシルチオニン / カテコール-O-メチル転移酵素 / COMT / 賦活化 / 腎機能障害 / 心血管系障害 / S-adenosylhomocystein / カテコール O- メチル転移酵素 / 賦活化物質 / カテコールO-メチル転位酵素 / 平衡透析 |
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| Outline of Final Research Achievements |
It is known that among end-stage renal disease and preeclampsia patients the progress of the disease accompany dysfunction of catechol O-methyl transferase activity. We hypothesized that inhibition by S-adenosylhomocystein (SAH) lowers COMT activity. We searched for compounds that release the enzyme from the inhibition, the enhancers. In this study we discovered an enhancer A00607 which is more potent ever. We intend to reveal the molecular mechanism how the enhancer removes the SAH inhibition by enzyme kinetic study, equilibrium dialusis and isothermal calorimetric titration method. We proposed a theoretical model (by-pass model) and built logical model to explain mechanism of enhancement.
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