26,27-双高-1α-羟基-和26,27-双高-24-表-1α,25-二羟基维生素D2类似物在体内的生物活性存在显著差异。

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.

作者信息

Perlman K L, Prahl J M, Smith C, Kutner A, DeLuca H F

机构信息

Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison 53706.

出版信息

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

PMID:7929052

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.

摘要

已合成26,27-二高-1α-羟基维生素D2、26,27-二高-24-表-1α-羟基维生素D2和26,27-二高-24-表-1α,25-二羟基维生素D2。与1α-羟基维生素D2和24-表-1α-羟基维生素D2不同，26,27-二高-1α-羟基维生素D2（1）和24-表类似物（2）在肠道钙转运、骨钙动员或骨骼矿化方面无活性。另一方面，26,27-二高-24-表-1α,25-二羟基维生素D2的生物活性与1,25-二羟基维生素D3相当。维生素D 25-羟化酶能轻易地将1α-羟基维生素D2转化为1,25-二羟基维生素D2。相比之下，相同制剂无法将26,27-二高-1α-羟基维生素D2和26,27-二高-24-表-1α-羟基维生素D2在碳25位进行羟化。因此，维生素D化合物碳26和碳27的同系化可能在空间上阻碍了维生素D 25-羟化酶。