摘要
维生素D3对于预防骨骼疾病、肌肉无力、自身免疫性疾病以及某些类型的癌症是必不可少的。维生素D3通过其代谢产物1α,25-二羟基维生素D_(3)[1,25(OH)_(2)D_(3)]充当转录因子维生素D受体(VDR)的有效激动剂。因此维生素D直接影响众多基因组位点及其靶组织的染色质结构和基因调控。近年来单独或组合修饰1,25(OH)_(2)D_(3)的侧链、A环、三烯系统或C环以及非甾体模拟物,均获得了多种有效的VDR激动剂和拮抗剂。目前为止,近150个VDR配体与各种维生素D类似物结合体的晶体结构已被逐渐阐明,使得这些化合物的作用机理明确至分子水平。本文综述了过去10年、尤其是近5年提出的重要维生素D类似物以及从有关VDR蛋白的新结构信息中得出的化合物分子水平的作用机理。
Vitamin D3 is essential for preventing bone diseases,muscle weakness,autoimmune diseases and some types of cancer.Vitamin D3 serves as a potent agonist of the transcription factor vitamin D receptor(VDR)through its metabolite 1α,25-dihydroxyvitamin D_(3)[1,25(OH)_(2)D_(3)].Therefore,vitamin D directly affects a number of genome sites,chromatin structures of targeted tissue and gene regulation.A variety of effective VDR agonists and certain antagonists have been obtained by solely and combinedly modifying the side chain of 1,25(OH)_(2)D_(3),A ring,triene system or C ring,as well as nonsteroidal mimetics.Nearly 150 crystal structures of a VDR ligand-binding domain with various vitamin D compounds have been gradually illuminated,which allows a molecular understanding of their action mechanisms.This review discusses the most important vitamin D analogs presented in the past 10 years and molecular mechanisms derived from new structural information related to the VDR protein.
作者
赵洺良
王明刚
刘振玉
孙桂玉
王清亭
杜昌余
陈阳生
ZHAO Mingliang;WANG Minggang;LIU Zhenyu;SUN Guiyu;WANG Qingting;DU Changyu;CHEN Yangsheng(CP Pharmaceutical Qingdao Co. Ltd.,Qingdao 266510, China)
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2021年第6期914-921,共8页
Chinese Journal of Osteoporosis
作者简介
通信作者:陈阳生,Email:chenys@cppqd.com。
