| Project/Area Number |
23590135
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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) |
2011 – 2013
|
| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ビタミンＤ / ビタミンＤ受容体 / アゴニスト / アンタゴニスト / パーシャルアゴニスト / 結晶構造 / 核内受容体 / ポケット構造 / 受容体 / 遺伝子転写 / アナログ / ビタミンD / ビタミンD受容体 |
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| Research Abstract |
To develop vitamin D receptor ligands which separate the various biological activities of 1a,25-dihydroxyvitamin D3, we focused on the structure of ligand-binding pocket of the receptor, especially the variable part of the pocket. As a result, we discovered vitamin D analogues with a branched side chain that induce structural rearrangement of the amino acid residues lining the ligand-binding pocket. These analogs showed agonistic, partial agonistic or antagonistic activities. By X-ray analysis, we found one of partial agonists exists in two conformations, namely agonist and antagonist conformations, in a single crystal.
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