26,27-Dihomo-1 alpha-hydroxy- and 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 analogs that differ markedly in biological activity in vivo

J Biol Chem. 1994 Sep 30;269(39):24014-9.

Abstract

26,27-Dihomo-1 alpha-hydroxyvitamin D2, 26,27-dihomo-24-epi-1 alpha-hydroxyvitamin D2, and 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 have been synthesized. In contrast to 1 alpha-hydroxyvitamin D2 and 24-epi-1 alpha-hydroxyvitamin D2, 26,27-dihomo-1 alpha-hydroxyvitamin D2 (1) and the 24-epi analog (2) have no activity in intestinal calcium transport, bone calcium mobilization, or skeleton mineralization. On the other hand, 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 is equal to 1,25-dihydroxyvitamin D3 in biological activity. Vitamin D 25-hydroxylase readily converts 1 alpha-hydroxyvitamin D2 to 1,25-dihydroxyvitamin D2. In contrast, the same preparations fail to hydroxylate 26,27-dihomo-1 alpha-hydroxyvitamin D2 and 26,27-dihomo-24-epi-1 alpha-hydroxyvitamin D2 on carbon 25. Thus, homologation of carbons 26 and 27 of the vitamin D compound likely sterically hinders vitamin D 25-hydroxylase.

Publication types

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

MeSH terms

  • Animals
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Calcium / metabolism
  • Ergocalciferols / chemistry
  • Ergocalciferols / pharmacology*
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Ion Transport / drug effects
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rickets / drug therapy
  • Structure-Activity Relationship

Substances

  • Ergocalciferols
  • Calcium