Conformationally Restricted Analogs of 1α,25-Dihydroxyvitamin D3 and Its 20-Epimer: Compounds for Study of the Three-Dimensional Structure of Vitamin D Responsible for Binding to the Receptor
Conformationally Restricted Analogs of 1α,25-Dihydroxyvitamin D3 and Its 20-Epimer: Compounds for Study of the Three-Dimensional Structure of Vitamin D Responsible for Binding to the Receptor
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1α,25-二羟基维生素 D3 及其 20-差向异构体的构象限制类似物：用于研究负责与受体结合的维生素 D 三维结构的化合物
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
S. Yamada
中科院分区：
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作者：
Keiko Yamamoto;Wei Yan Sun;M. Ohta;K. Hamada;H. F. Deluca;S. Yamada
两种蛋白质在维生素D功能的表达中起重要作用：特异性核受体蛋白（维生素D受体，VDR）和转运蛋白（维生素D结合蛋白，DBP）。本研究旨在阐明负责与这些蛋白质结合的维生素D的构象。为此，通过系统的构象搜索分析了1，25（OH）2D 3（1）及其20-差向异构体20-epi-1，25（OH）2D 3（2）的侧链迁移率。结果被描绘为三维点图，这表明两种维生素（1和2）的侧链占据在两个区域中分开的不同空间区域。我们将这些区域表示为A和G（1）和EA和EG（2）。设计了四种类似物，即22-甲基化的1，25（OH）2D 3的C（20）和C（22）（3−6）非对映异构体，其侧链分别被限制为占据G、A、EA和EG。这些类似物（3 - 6）是通过有机铜酸酯与甾体E-和Z-2的立体选择性共轭加成有效合成的。
Two proteins play important roles in the expression of vitamin D function: the specific nuclear receptor protein (vitamin D receptor, VDR) and the transport protein (vitamin D binding protein, DBP). This study was conducted to clarify the conformation of vitamin D responsible for binding to those proteins. For the purpose, the side chain mobility of 1,25(OH)2D3 (1) and its 20-epimer, 20-epi-1,25(OH)2D3 (2), was analyzed by a systematic conformational search. The results were depicted as a three-dimensional dot map, which indicates that the side chains of the two vitamins (1 and 2) occupy different spatial regions that are separated in two areas. We denoted these areas as A and G for 1 and EA and EG for 2. Four analogs, the diastereomers at C(20) and C(22) (3−6) of 22-methylated 1,25(OH)2D3 whose side chains were confined to occupy G, A, EA, and EG, respectively, were designed. These analogs (3−6) were synthesized efficiently by a stereoselective conjugate addition of organocuprate to steroidal E- and Z-2...