2 alpha-(3-hydroxypropyl)- and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 accessible to vitamin D receptor mutant related to hereditary vitamin D-resistant rickets.
Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder caused by mutations in the vitamin D receptor, which lead to resistance to 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)]. We found that the A ring-modified analogues, 2alpha-(3-hydroxypropyl)- and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)(2)D(3), (O1C3 and O2C3) can bind better than the natural hormone to the mutant VDR (R274A), which similar to the HVDRR mutant, R274L, had lost the hydrogen bond to the 1alpha-hydroxyl group of 1alpha,25(OH)(2)D(3).
Kittaka
Atsushi
A
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Kurihara
Masaaki
M
Peleg
Sara
S
Suhara
Yoshitomo
Y
Takayama
Hiroaki
H
D006860:Hydrogen Bonding; D007015:Hypophosphatemia, Familial / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000235:genetics* / Q000378:metabolism
D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D