Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure-activity assessment
Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure-activity assessment
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DOI：
10.1016/j.etap.2007.10.017
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发表时间：
2008-03-01
影响因子：
4.3
通讯作者：
Robertson, Larry W.
中科院分区：
文献类型：
--
作者：
Luthe, Gregor;Jacobus, James A.;Robertson, Larry W.
关于多氯联苯（PCBs）与转录因子（受体）相互作用的大量文献对于理解相似性和区别以及关于多溴联苯醚（PBDEs）对这些受体的活性的假设具有重要价值。我们的目标是对PBDE对AhR、CAR、PXR、ER、AR、PR、DHT、TH、T3、T4和IGF的影响以及PPAR、RyR、GR和GABA的假设生物活性进行最全面的概述。除了对配体构象的影响外，我们还讨论了配体的结构对结合亲和力的影响：大小和极化性、亲水性、吉布斯溶剂化自由能、诱导和中间体效应。我们评估了确定这些卤化烃生物相关构象的技术，包括计算方法，x射线和微波光谱。一种新的氟标记配体方法有望作为阐明配体-受体相互作用中的空间和电子效应的工具。根据我们的评估，我们预测多溴二苯醚本身不表现出AhR活性，但杂质是造成这些影响的原因。(C) 2007 Elsevier B.V.版权所有
The extensive body of literature regarding the interaction of polychlorinated biphenyls (PCBs) with transcription factors (receptors) has great value to understand similarities and distinctions and in formulating hypotheses regarding the activity of polybrominated diphenyl ethers (PBDEs) toward those same receptors. Our goal is to present the most comprehensive overview of PBDE effects on AhR, CAR, PXR, ER, AR, PR, DHT, TH, T3, T4 and IGF, as well as hypothetical biological activities of PPAR, RyR, GR and GABA. Aside the influence of the conformation of the ligand, we discuss its constitution influencing the binding affinity: size and polarizability, hydrophilicity, Gibbs free energy of solvation, inductive and mesomeric effects. We evaluate the techniques to determine the biologically relevant conformation of these halogenated hydrocarbons, including computation methods, X-ray and microwave spectroscopy. A novel fluoro-tagged ligand approach holds promise as tools for illuminating the steric and electronic effects in ligand-receptor interaction. Based on our assessment, we predict that PBDEs do not exhibit AhR activity themselves, but impurities are responsible for these effects. (C) 2007 Elsevier B.V. All rights reserved.