title: Design, synthesis and X-ray crystallographic study of new nonsecosteroidal vitamin D receptor ligands.
abstract: 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.
authors: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors: Yosuke
authors: Y
authors: Demizu
authors: Takeo
authors: T
authors: Takahashi
authors: Fumiya
authors: F
authors: Kaneko
authors: Yukiko
authors: Y
authors: Sato
authors: Haruhiro
authors: H
authors: Okuda
authors: Eiji
authors: E
authors: Ochiai
authors: Kyohei
authors: K
authors: Horie
authors: Ken-Ichiro
authors: K
authors: Takagi
authors: Shinji
authors: S
authors: Kakuda
authors: Midori
authors: M
authors: Takimoto-Kamimura
authors: Masaaki
authors: M
authors: Kurihara
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D051381:Rats; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D018167:Receptors, Calcitriol