药物与人血清白蛋白共价加合物的鉴定研究进展

Advancements in the identification of adducts of drug-human serum albumin

药物及其代谢物与蛋白质的共价结合形成药物-蛋白质加合物,可能导致机体的不良反应。加合物组学技术的进展,有助于系统研究药物与人血浆蛋白的共价加合。对于许多药物而言,如β-内酰胺抗生素、酰基葡萄糖苷酸、共价酪氨酸激酶抑制剂及反应性代谢物,人血清白蛋白是形成药物-蛋白质加合物的潜在靶标和生物标志物。本综述将叙述相关的技术进展,阐述药物与人血清白蛋白共价加合物的鉴定方法,定义形成加合物的化学反应,并初步探讨药物与人血清白蛋白共价加合在药物不良反应中的作用以及对药动学的潜在影响。

The covalent binding of drugs and their metabolites to proteins forms drug-protein adducts,which may cause adverse reactions in the body.The development of adductomics technology is helpful for the identification of covalent adducts between drugs and human plasma proteins.For many drugs,such as beta-lactam antibiotics,acyl glucuronides,covalent tyrosine kinases inhibitors,and reactive metabolites,human serum albumin(HSA)is a potential target and biomarker for the formation of drug-protein adducts.In this review,we will describe the relevant technical advances,describe the methods for the identification of covalent adducts of drugs and HSA,define the chemical reactions that form adducts,and preliminarily explore the role of drug-HSA adducts in adverse drug reactions and the potential effect on pharmacokinetics.