Laboratory of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Acta Pharmacol Sin. 2013 Aug;34(8):998-1006. doi: 10.1038/aps.2013.78. Epub 2013 Jul 15.
Chiral drugs show distinct biochemical and pharmacological behaviors in the human body. The binding of chiral drugs to plasma proteins usually exhibits stereoselectivity, which has a far-reaching influence on their pharmacological activities and pharmacokinetic profiles. In this review, the stereoselective binding of chiral drugs to human serum albumin (HSA), α1-acid glycoprotein (AGP) and lipoprotein, three most important proteins in human plasma, are detailed. Furthermore, the application of AGP variants and recombinant fragments of HSA for studying enantiomer binding properties is also discussed. Apart from the stereoselectivity of enantiomer-protein binding, enantiomer-enantiomer interactions that may induce allosteric effects are also described. Additionally, the techniques and methods used to determine drug-protein binding parameters are briefly reviewed.
手性药物在人体内表现出明显的生化和药理学行为。手性药物与血浆蛋白的结合通常表现出立体选择性，这对它们的药理学活性和药代动力学特征有深远的影响。在这篇综述中，详细介绍了手性药物与人血清白蛋白（HSA）、α1-酸性糖蛋白（AGP）和脂蛋白这三种人血浆中最重要的蛋白质的立体选择性结合。此外，还讨论了应用 AGP 变体和 HSA 的重组片段研究对映体结合特性。除了对映体-蛋白结合的立体选择性外，还描述了可能诱导变构效应的对映体-对映体相互作用。此外，还简要回顾了用于确定药物-蛋白结合参数的技术和方法。
