Design, Synthesis, and Structure-activity Relationship Study of Organoantimony Compounds That Induce the Expression of Perlecan in Vascular Endothelial Cells

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  • Naka Hiroyuki
    Faculty of Pharmaceutical Sciences, Tokyo University of Science Adovanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science, and Elements Chemistry Laboratory, RIKEN
  • Takita Ryo
    Adovanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science, and Elements Chemistry Laboratory, RIKEN Graduate School of Pharmaceutical Sciences, The University of Tokyo
  • Kaji Toshiyuki
    Faculty of Pharmaceutical Sciences, Tokyo University of Science Division of Bio-organometallics, Research Institute of Science and Technology, Tokyo University of Science
  • Uchiyama Masanobu
    Adovanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science, and Elements Chemistry Laboratory, RIKEN Graduate School of Pharmaceutical Sciences, The University of Tokyo Division of Bio-organometallics, Research Institute of Science and Technology, Tokyo University of Science

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Other Title
  • 内皮細胞のパールカンの発現を誘導する有機アンチモン化合物の設計・合成・機能解析と構造活性相関研究
  • Symposium Review : 内皮細胞のパールカンの発現を誘導する有機アンチモン化合物の設計・合成・機能解析と構造活性相関研究
  • Symposium Review : ナイヒ サイボウ ノ パールカン ノ ハツゲン オ ユウドウ スル ユウキ アンチモン カゴウブツ ノ セッケイ ・ ゴウセイ ・ キノウ カイセキ ト コウゾウ カッセイ ソウカン ケンキュウ

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Abstract

  Organometallic compounds and complexes possibly show novel bioactivities unprecedented with organic molecules that consist of C, H, O, and N atoms. We have already reported that an organoantimony compound selectively induces the expression of perlecan, a large heparin sulfate proteoglycan, in cultured vascular endothelial cells. Perlecan consists of a core protein with Mr of approximately 400 kDa and three anticoagulant heparan sulfate glycosaminoglycan chains. However, little is known about the molecular mechanisms of perlecan expression in endothelial cells. Since an organoantimony compound induces the expression of perlecan, we prepared a variety of its derivatives and tried to identify the binding proteins for the organoantimony compound by the drug affinity responsive target stability method, a negative selection method to identify the target proteins. As the results, we found glucocoriticoid receptor as binding protein of the organoantimony compound, which mediates the expression of perlecan in endothelial cells.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 134 (7), 789-791, 2014-07-01

    The Pharmaceutical Society of Japan

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