title: New C15-substituted active vitamin D3.
abstract: C15-Substituted 1α,25-dihydroxyvitamin D(3) analogs were synthesized for the first time to investigate the effects of the modified CD-ring on biological activity concerning the agonistic positioning of helix-3 and helix-12 of the vitamin D receptor (VDR). X-ray cocrystallographic analysis proved that 0.6 Å shifts of the CD-ring and shrinking of the side chain were necessary to maintain the position of the 25-hydroxy group for proper interaction with helix-12. The 15-hydroxy-16-ene derivative showed higher binding affinity for hVDR than the natural hormone.
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Shindo
authors.forename: Go
authors.initials: G
authors.lastname: Kumagai
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawada
authors.forename: Nozomi
authors.initials: N
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Shinji
authors.initials: S
authors.lastname: Kakuda
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Takagi
authors.forename: Eiji
authors.initials: E
authors.lastname: Ochiai
authors.forename: Kyohei
authors.initials: K
authors.lastname: Horie
authors.forename: Midori
authors.initials: M
authors.lastname: Takimoto-Kamimura
authors.forename: Seiichi
authors.initials: S
authors.lastname: Ishizuka
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takenouchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
mesh_terms: D002117:Calcitriol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D018167:Receptors, Calcitriol / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol; D002117:Calcitriol