Systematic synthesis and functional analysis of vitamin D receptor cofactor peptides
| Project/Area Number |
17K08373
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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) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ビタミンD / ビタミンD受容体 / コファクター / コアクチベーター / コリプレッサー / 結晶構造解析 / ビタミンＤ / 核内受容体 / ビタミンＤ受容体 / 合成リガンド / アゴニスト / アンタゴニスト / X線結晶構造解析 |
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| Outline of Final Research Achievements |
A series of co-factor peptides for vitamin D receptor were comprehensively synthesized by microwave-assisted solid-phased synthesis method. Among them, co-activator peptides, SRC2-2 and RIP140-5, were succeeded in X-ray crystal structural analysis of the complex with vitamin D receptor ligand-binding domain (VDR-LBD). In analysis using surface plasmon resonance (SPR), RIP140-5 showed higher affinity for VDR-LBD than DRIP205-1 which is a co-activator peptide most used for the crystal structural analysis of VDR-LBD. Furthermore, we found that, in co-repressor peptide, the elongation from 13 to 19 amino acid residues increases the affinity for VDR-LBD.
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| Academic Significance and Societal Importance of the Research Achievements |
核内受容体の一員であるビタミンD受容体（VDR）のコファクターペプチドを網羅的に合成し、ビタミンD受容体リガンド結合ドメイン (VDR-LBD)の結晶構造解析に有用なRIP140-5を見出したことは、これまで困難であったVDR-LBDとリガンドの組み合わせの共結晶構造の解析に貢献すると期待できる。核内受容体LBDは制御機構に共通点が多いため、本研究成果は、VDRのみにとどまらず、他の核内受容体の新規構造解析にもつながるものである。
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Report
(4 results)
Research Products
(9 results)
