Development of reversible covalent vitamin D receptor ligands
| Project/Area Number |
26460155
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | Showa Pharmaceutical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | ビタミンＤ / ビタミンＤ受容体 / 共有結合型リガンド / ビタミンD受容体 / 共有結合 / ESI-MS / 結晶構造解析 / マイケル付加 / ビタミンD |
|---|
| 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.
|
Report
(4 results)
Research Products
(9 results)
