细胞色素P450酶电化学生物传感器的构建及其药物代谢应用

Fabrication and Application of Cytochrome P450 Electrochemcial Biosensor in Drug Metabolism

药物代谢过程是药物在体内产生药效和毒性的主要过程,发展廉价、方便、快速、高通量的体外药物代谢研究方法对新药的开发和设计、给药的方法和剂量、临床药物的检测等都有重要的指导意义.细胞色素P450酶(CYP450酶)在药物的I相反应中起到关键作用,以电极代替辅酶NADPH提供CYP450酶催化反应过程中需要的两个电子,构建CYP450酶电化学生物传感器可实现药物的初步筛选.大量研究表明,CYP450酶在电极表面合适的固定方法与电极材料可有效提高传感器的检测性能.本文主要综述近年来CYP450酶电化学生物传感器的构建及其在药物代谢研究方面的应用,并展望其研发前景.

The process of drug metabolism plays an important role in drug efficacy and toxicity in vivo. Thus, the development of cheap, continent, rapid and high-throughput method for drug metabolism studies has great guiding significance for the design of new drugs, the determination of drug dosage and the detection of clinical drugs. Since the key role played by Cytochrome P450 （CYP450） in phase-I drug reaction, the constructed CYP450 enzyme biosensor can be used for the initial screening of drugs. It is found that the replacement of coenzyrne NADPH with an electrode is to provide two electrons demanded in the catalytic reaction. Furthermore, the assembly methods and electrode materials have a close relationship with the detection performance of the constructed CYP450 biosensors. In this review, the construction methods of CYP450 electrochemical biosensor and their applications in drug metabolism are summarized. Particularly, future study and prospect of development are envisioned.