Efficient and versatile synthesis of novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D(3) analogues and their docking to vitamin D receptors.
Novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D(3) analogues with 2alpha-alkyl and 2alpha-hydroxyalkyl groups were systematically synthesized from D-xylose. Their conformation on binding to the ligand binding domain (LBD) of the vitamin D receptor was analyzed. It has been found that the 2alpha-hydroxypropyl group best fits the cavity of the LBD, and the binding activity is three times higher than that for the natural hormone.
Suhara
Y
Y
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan.
Nihei
K I
KI
Kurihara
M
M
Kittaka
A
A
Yamaguchi
K
K
Fujishima
T
T
Konno
K
K
Miyata
N
N
Takayama
H
H
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D018167:Receptors, Calcitriol / Q000737:chemistry*
D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol