Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
Bioorg Med Chem Lett. 2011 Oct 15;21(20):6104-7. doi: 10.1016/j.bmcl.2011.08.047. Epub 2011 Aug 17.
We designed and synthesized nonsecosteroidal vitamin D receptor (VDR) ligands that formed H-bonds with six amino acid residues (Tyr143, Ser233, Arg270, Ser274, His301 and His393) of the VDR ligand-binding domain. The ligand YR335 exhibited potent transcriptional activity, which was comparable to those of 1α,25-dihydroxyvitamin D(3) and YR301. The crystal structure of the complex formed between YR335 and the VDR ligand-binding domain was solved, which revealed that YR335 formed H-bonds with the six amino acid residues mentioned above.
我们设计并合成了非甾体维生素 D 受体（VDR）配体，这些配体与 VDR 配体结合域的六个氨基酸残基（Tyr143、Ser233、Arg270、Ser274、His301 和 His393）形成氢键。配体 YR335 表现出很强的转录活性，与 1α,25-二羟维生素 D(3)和 YR301 相当。我们解析了 YR335 与 VDR 配体结合域形成的复合物的晶体结构，结果表明 YR335 与上述六个氨基酸残基形成氢键。
