Based on human estrogen receptor α ligand binding domain (hERα-LBD) as recognition element, a fluorescence polarization assay was developed for the determination of bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and their derivatives. Fluorescence polarization assay showed that BADGE, BFDGE and their derivatives exhibited dose-dependent binding to the receptor protein. The results of reporter gene assay indicated that all the tested bisphenol diglycidyl ethers show no agonistic activities, but some of them exhibit anti-estrogenic activities toward ERα. All the tested bisphenol diglycidyl ethers fitted into the hydrophobic binding pocket and adopted the conformation that resembled 4-hydroxytamoxifen, a selective antagonist of ERα. Quantitative structure-activity relationship analysis showed that the binding potencies of bisphenol diglycidyl ethers with hERα-LBD might be structure-dependent. This work may provide insight into the in silico screening of ER ligands from unsuspected chemicals.

中文翻译：

---

双酚二缩水甘油醚与雌激素受体 α 的相互作用：荧光偏振、报告基因和分子建模研究

以人雌激素受体α配体结合域（hERα-LBD）为识别元件，建立了荧光偏振法测定双酚A二缩水甘油醚（BADGE）、双酚F二缩水甘油醚（BFDGE）及其衍生物。荧光偏振试验表明BADGE、BFDGE 及其衍生物与受体蛋白呈剂量依赖性结合。报告基因检测结果表明，所有测试的双酚二缩水甘油醚均不显示激动活性，但其中一些对ERα表现出抗雌激素活性。所有测试的双酚二缩水甘油醚都安装在疏水结合口袋中，并采用类似于 4-羟基三苯氧胺（ERα 的选择性拮抗剂）的构象。定量构效关系分析表明，双酚二缩水甘油醚与hERα-LBD的结合效力可能具有结构依赖性。这项工作可能有助于深入了解来自未知化学品的 ER 配体的计算机筛选。