title: Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor.
abstract: In the study of the synthesis of 14-epi-19-norprevitamin D(3), 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 1α,25(OH)(2)D(3).
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1, Suwarashi, Sagamihara, Kanagawa 252-5195, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawada
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tsukuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Shinji
authors.initials: S
authors.lastname: Kakuda
authors.forename: Midori
authors.initials: M
authors.lastname: Takimoto-Kamimura
authors.forename: Eiji
authors.initials: E
authors.lastname: Ochiai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takenouchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
mesh_terms: D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D007536:Isomerism; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000737:chemistry*
chemical_list: D008024:Ligands; D018167:Receptors, Calcitriol; D002762:Cholecalciferol; C025168:previtamin D(3)