核内受容体リガンドの合成とハイスループットな評価法によるリガンド－受容体－転写共役因子複合体の解析；生理活性メカニズムの新知見

DOI

書誌事項

タイトル別名
  • A New High-throughput Analyzing System of Ligand Induced Cofactor Recruitment on Vitamin D Receptor; Synthesis and Biological Evaluation of 19-Norvitamin D3 Derivatives

抄録

Synthesis of 25-hydroxy-19-norvitamin D3 derivatives as prohormone type agents for anti-prostate diseases was accomplished utilizing Julia-type olefination. The compounds showed potent antiproliferative activity on an immortalized normal prostate cell line, PZ-HPV-7. We demonstrated that 25-hydroxy-19-norvitamin D3 was hydroxylated to form 1?,25-dihydroxy-19-norvitamin D3 by human 1?-hydroxylase (CYP27B1) in a cell-free system. Moreover, we have developed a novel rapid analyzing system of ligand induced cofactor recruitment on vitamin D receptor (VDR) using fluorophore labeled coactivator (CoA) and HCHO fixing of the complex. Recruitment of CoA by 19-norvitamin D3 derivatives was analyzed using this system in a high-throughput manner. Efficiency of recruiting of CoA would explain discrepancy between strong biological activity and weak VDR binding affinity of ligands.

収録刊行物

キーワード

詳細情報 詳細情報について

  • CRID
    1390001205634165504
  • NII論文ID
    130006996415
  • DOI
    10.14895/hannou.31.0.4.0
  • データソース種別
    • JaLC
    • CiNii Articles
  • 抄録ライセンスフラグ
    使用不可

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