Kittaka Atsushi, Kurihara Masaaki, Peleg Sara, Suhara Yoshitomo, Takayama Hiroaki
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Chem Pharm Bull (Tokyo). 2003 Mar;51(3):357-8. doi: 10.1248/cpb.51.357.
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).
遗传性维生素D抵抗性佝偻病（HVDRR）是一种由维生素D受体突变引起的遗传性疾病，该突变导致对1α,25-二羟基维生素D3 [1α,25(OH)2D3]产生抵抗。我们发现，A环修饰的类似物，2α-(3-羟丙基)-和2α-(3-羟丙氧基)-1α,25(OH)2D3（O1C3和O2C3）与天然激素相比，能更好地与突变型维生素D受体（R274A）结合，该突变型与HVDRR突变体R274L相似，已失去与1α,25(OH)2D3的1α-羟基的氢键。
