A theoretical study of the binding of polychlorinated biphenyls (PCBs), dibenzodioxins, and dibenzofuran to human plasma prealbumin.
A theoretical study of the binding of polychlorinated biphenyls (PCBs), dibenzodioxins, and dibenzofuran to human plasma prealbumin.
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多氯联苯 (PCB)、二苯并二恶英和二苯并呋喃与人血浆前白蛋白结合的理论研究。
DOI：
10.1021/jm00162a006
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发表时间：
1986
影响因子：
7.3
通讯作者：
McKinney,JD
中科院分区：
文献类型：
--
作者：
Pedersen,LG;Darden,TA;Oatley,SJ;McKinney,JD
结合能的人血浆前白蛋白使用能量最小化程序琥珀被发现的一系列多氯联苯，二苯并二恶英，和二苯并呋喃。氯代类似物的溶剂化自由能的校正导致复杂的形成的微分自由能的估计。在许多情况下，将这些值与已知的实验log（Kkb/KK（））值进行比较。该理论正确地区分了强、中间和非粘合剂。在计算的基础上，预测2，3，7，8-四氯二苯并二恶英和2，3，7，8-四氯二苯并呋喃是强结合剂，预测3，3 '，5，5'-四氯二苯醌是弱结合剂，预测八氯二苯并二恶英根本不结合。前白蛋白相互作用的这一理论模型可能是用于估计多氯联苯和相关的卤代芳烃的环境重要性的潜在毒性。分布的多氯联苯（PCBs），二苯并二恶英，二苯并呋喃在环境中构成了一个潜在的严重的公共卫生问题。几起事故1 -3有助于将与这些化合物和相关化合物有关的关注集中在其毒性作用的分子机制上。例如，现在已知这些化合物与胞质受体结合，从而明显增强某些与致癌行为有关的酶的活性。4最近，我们发现5羟基化的多氯联苯增加了溶解度，将定量取代甲状腺素（[125 I]甲状腺素）与前白蛋白（主要甲状腺素（T4）转运蛋白之一）的复合物。从这些数据中，我们已经能够确定多氯联苯结合前白蛋白的平衡常数，以及验证甲状腺素-前白蛋白
Binding energies to human plasma prealbumin using the energy minimization program amber are found for a series of polychlorinated biphenyls, dibenzodioxins, and dibenzofuran. Corrections for solvation free energies of the chlorinated analogues lead to estimates of the differential free energies of complex formation. These are compared in a number of cases to known experimental log {Kkb/KK {) values. The theory correctly separates strong, intermediate, and nonbinders. On the basis of calculations, 2, 3, 7, 8-tetrachlorodibenzodioxinand 2, 3, 7, 8-tetrachlorodibenzofuran are predicted to be strong binders, 3, 3', 5, 5'-tetrachlorodiphenoquinone is predicted to be a weak binder, and octachlorodibenzodioxin is predicted to not bind at all. This theoretical model for prealbumin interactions may be of use in estimating the toxic potential of PCBs and related halogenated aromatic hydrocarbons of environmental importance.The distribution of polychlorinated biphenyls (PCBs), dibenzodioxins, and dibenzofurans in the environment constitutes a potentially serious public health problem. Several accidents1-3 have helped to focus the concern relating to these and related compounds on their molecular mechanism of toxic action. It is now known, for instance, that the compounds bind to cytosolic receptors and thereby apparently enhance the activity of certain enzymes implicated in carcinogenicbehavior. 4 Recently, we have shown5 that PCBs hydroxylated to increase solubility will quantitatively displace thyroxine ([125I] thyroxine) from its complex with prealbumin, one of the majorthyroxine (T4) transport proteins. From this data we have been able to determine equilibrium constants for PCBs binding to prealbumin as well as verify the thyroxine-prealbumin