Homogeneous assay for zearalenone analogues and their docking studies with apo-/holo-estrogen receptors

文献类型： 外文期刊

第一作者： Song, Yifan

作者： Song, Yifan;Guan, Tianzhu;Zhang, Tiehua;Wu, Wenfu;Hou, Ligang;Li, Tiezhu;Wang, Yongjun

作者机构：

期刊名称：ANALYTICAL METHODS （ 影响因子：2.896； 五年影响因子：2.716 ）

ISSN： 1759-9660

年卷期： 2019 年 11 卷 2 期

页码：

收录情况： SCI

摘要： A solution-based homogeneous assay with fluorescence polarization combined with receptor recognition was developed for the determination of zearalenone analogues (zeranols). Firstly, a recombinant human estrogen receptor ligand binding domain (hER-LBD) was expressed as a soluble protein in Escherichia coli BL21(DE3)pLysS. In the fluorescence polarization assay, hER-LBD and coumestrol were employed as the recognition element and fluorescent tracer, respectively. Zearalenone and its derivatives exhibit dose-dependent binding to hER-LBD, suggesting that the proposed method can potentially be applied for high-throughput monitoring of multiple zeranols. In addition, the structural basis for the estrogenicity of zeranols was demonstrated by molecular docking studies. From a structural point of view, zeranols share a similar orientation and binding mode to those observed for 17-estradiol, an endogenous estrogen. Comparison of the docking scores with the apo and holo forms of hER-LBD shows that zeranols in the agonistic receptor conformation exhibit higher binding energies than those in other conformations. Both hydrophobic and hydrogen-bonding interactions are the dominant forces to stabilize binding of zeranols in the pocket. Structure-activity relationship analysis suggests that the keto/hydroxyl group and the trans double bond of the macrolide ring, as well as the two hydroxyl groups of the aromatic ring, are critical functional groups participating in the zeranols-hER-LBD binding. These results suggest the possibility to employ molecular modeling techniques to preliminarily evaluate the estrogenic potency of potential xenoestrogens. In summary, this work may provide an understanding of the molecular mechanism involved in zeranols-hER-LBD binding interactions.

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