2016 Fiscal Year Final Research Report
Development of reversible covalent vitamin D receptor ligands
| Project/Area Number |
26460155
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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 | Showa Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | ビタミンＤ / ビタミンＤ受容体 / 共有結合型リガンド |
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| Outline of Final Research Achievements |
As a ligand which reversibly covalently binds to the vitamin D receptor, a ligand having a second electron withdrawing group at the α position of Michael acceptor was designed. First, a derivative having a cyano group in addition to a carbonyl group in the side chain of lithocholic acid was synthesized. Subsequently, a derivative having a carbonyl group and a cyano group in the side chain of vitamin D was synthesized. Covalent bond formation between the synthetic vitamin D derivative and the receptor was examined using ESI-MS, but no covalent bond was observed. On the other hand, details of the formation of covalent bonds between vitamin D derivatives having an enone group in the side chains and the receptor, which triggered this research project, were confirmed by ESI-MS analysis and X-ray crystal structure analysis.
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| Free Research Field |
タンパク質の立体構造に基づいたリガンド創製
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