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

Chem Pharm Bull (Tokyo). 2003 Mar;51(3):357-8. doi: 10.1248/cpb.51.357.

Abstract

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).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Hydrogen Bonding
  • Hypophosphatemia, Familial / genetics*
  • Hypophosphatemia, Familial / metabolism*
  • Mutation*
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / metabolism
  • Vitamin D / analogs & derivatives*
  • Vitamin D / chemistry
  • Vitamin D / genetics*
  • Vitamin D / metabolism
  • Vitamin D Deficiency / genetics*
  • Vitamin D Deficiency / metabolism

Substances

  • Receptors, Calcitriol
  • dihydroxy-vitamin D3
  • Vitamin D