2010 Fiscal Year Final Research Report
Role of ligands for allosteric network of nuclear receptors
| Project/Area Number |
20590108
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 |
YAMAMOTO Keiko Showa Pharmaceutical University, 薬学部, 教授 (90147017)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Yuki 昭和薬科大学, 薬学部, 助教 (00297045)
ITOH Toshimasa 昭和薬科大学, 薬学部, 助教 (80536110)
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| Project Period (FY) |
2008 – 2010
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| Keywords | ビタミンD / ビタミンD受容体 / PPAR / 転写因子 / 結晶構造 / コンフォメーション変化 / シグナリング / 骨粗鬆症 |
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| Research Abstract |
Active vitamin D derivatives with 22-butyl substituent were found to be a new class of agonists and antagonists inducing the different pocket structure of the vitamin D receptor. Next, we synthesized vitamin D derivatives with 22-alkyl substituent and performed their SAR study. Then we tried X-ray crystallographic analysis of the complex of vitamin D receptor and ligand with particular activity. These results indicate that a ligand determines position of helix 12 via allosteric network and consequently expresses its particular activity.
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