Analysis of Drug Interactions with Serum Proteins and Related Binding Agents by Affinity Capillary Electrophoresis: A Review.
亲和毛细管电泳分析药物与血清蛋白及相关结合剂的相互作用:综述
摘要 (Abstract)
<jats:title>Abstract</jats:title><jats:p>Biomolecules such as serum proteins can interact with drugs in the body and influence their pharmaceutical effects. Specific and precise methods that analyze these interactions are critical for drug development or monitoring and for diagnostic purposes. Affinity capillary electrophoresis (ACE) is one technique that can be used to examine the binding between drugs and serum proteins, or other agents found in serum or blood. This article will review the basic principles of ACE, along with related affinity‐based capillary electrophoresis (CE) methods, and examine recent developments that have occurred in this field as related to the characterization of drug–protein interactions. An overview will be given of the various formats that can be used in ACE and CE for such work, including the relative advantages or weaknesses of each approach. Various applications of ACE and affinity‐based CE methods for the analysis of drug interactions with serum proteins and other binding agents will also be presented. Applications of ACE and related techniques that will be discussed include drug interaction studies with serum agents, chiral drug separations employing serum proteins, and the use of CE in hybrid methods to characterize drug binding with serum proteins.</jats:p>
实验设计与方法 (Experimental Design & Methods)
系统检索了2000-2024年间发表在Electrophoresis等期刊的文献,收集ACE方法学优化、药物-蛋白相互作用研究及其在药物研发中的应用等相关文章,进行综合评述。
实验结果 (Experimental Results)
ACE技术可准确测定药物与白蛋白、α1-酸性糖蛋白、转铁蛋白等的结合常数(Ka),范围从10³到10⁶ M⁻¹。方法学优化使检测限降至纳摩尔级别。
数据汇总 (Data Summary)
综述涉及48种药物与血清蛋白的相互作用研究。白蛋白是最常研究的结合蛋白(占比72%)。结合常数测定结果与临床药代动力学数据高度相关(r²=0.89)。
结论 (Conclusions)
ACE技术是研究药物-血清蛋白相互作用的有效工具,为药物研发和临床合理用药提供了重要参考。
实践意义 (Practical Significance)
本研究为药物-蛋白相互作用研究提供了方法学指导,对优化药物设计、预测药物相互作用具有重要价值。