Development of 14-epi-19-Nortachysterol and Its Unprecedented Binding Configuration for the Human Vitamin D Receptor

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• 作者：Daisuke Sawada ; Yuya Tsukuda ; Hiroshi Saito ; Shinji Kakuda ; Midori Takimoto-Kamimura ; Eiji Ochiai ; Kazuya Takenouchi ; Atsushi Kittaka
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：May 11, 2011
• 年：2011
• 卷：133
• 期：18
• 页码：7215-7221
• 全文大小：973K
• 年卷期：v.133,no.18(May 11, 2011)
• ISSN：1520-5126

文摘

In the study of the synthesis of 14-epi-19-norprevitamin D₃, we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19-nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1伪,25(OH)₂D₃.