2 α-(3-hydroxypropyl)- and 2 α-(3-hydroxypropoxy)-1 α,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 1 α,25-dihydroxyvitamin D₃ [1 α,25(OH)₂D ₃]. We found that the A ring-modified analogues, 2 α-(3-hydroxypropyl)-and 2 α-(3-hydroxypropoxy)-1 α,25(OH) ₂D₃, (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 1 α-hydroxyl group of 1 α,25(OH) ₂D₃.