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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).

chemical and pharmaceutical bulletin/chemical and pharmaceutical bulletin

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.