Department of Chemistry, University of Nebraska, Lincoln, NE 68588-0304, USA.
Curr Drug Metab. 2011 May;12(4):313-28. doi: 10.2174/138920011795202938.
The binding of drugs with serum proteins can affect the activity, distribution, rate of excretion, and toxicity of pharmaceutical agents in the body. One tool that can be used to quickly analyze and characterize these interactions is high-performance affinity chromatography (HPAC). This review shows how HPAC can be used to study drug-protein binding and describes the various applications of this approach when examining drug interactions with serum proteins. Methods for determining binding constants, characterizing binding sites, examining drug-drug interactions, and studying drug-protein dissociation rates will be discussed. Applications that illustrate the use of HPAC with serum binding agents such as human serum albumin, α(1)-acid glycoprotein, and lipoproteins will be presented. Recent developments will also be examined, such as new methods for immobilizing serum proteins in HPAC columns, the utilization of HPAC as a tool in personalized medicine, and HPAC methods for the high-throughput screening and characterization of drug-protein binding.
药物与血清蛋白的结合会影响药物在体内的活性、分布、排泄速率和毒性。一种可用于快速分析和描述这些相互作用的工具是高效亲和色谱（HPAC）。本文综述了 HPAC 如何用于研究药物-蛋白结合，并描述了在考察药物与血清蛋白相互作用时，该方法的各种应用。将讨论用于确定结合常数、描述结合部位、考察药物-药物相互作用以及研究药物-蛋白解离速率的方法。将介绍说明使用 HPAC 与血清结合剂（如人血清白蛋白、α(1)-酸性糖蛋白和脂蛋白）的应用。还将研究最近的进展，例如在 HPAC 柱中固定血清蛋白的新方法、将 HPAC 用作个体化医学工具，以及用于高通量筛选和描述药物-蛋白结合的 HPAC 方法。
