质谱在金属抗癌药物与蛋白质相互作用研究中的应用

研究细胞毒性金属抗肿瘤药物与蛋白质的相互作用,以及这种相互作用对药物的细胞摄入、转运、代谢和生物利用度的影响,对金属抗癌药物的结构设计和优化,提高药物的抗癌活性,降低毒副作用具有重要意义。基于软电离技术的电喷雾质谱和基质辅助激光解析电离质谱能够在分析检测过程中很好的保留金属抗癌药物与蛋白质的共价(配位)结合,获得药物与蛋白质结合位点的信息。同时,质谱分析还具有灵敏度高,所需样品量少,耗时短以及适用于分析复杂生物样品等优点,已成为研究金属抗癌药物与蛋白质相互作用最强有力的工具,在为药物发现提供大量化学、生物信息的同时,也极大地促进了质谱技术自身的发展。本文将结合我们在金属抗癌药物相互作用组学研究中取得的最新进展,系统地总结、评述Bottom-up和Top-down质谱分析方法在铂、钌类金属抗癌药物与蛋白质相互作用研究中的发展动态,并分析这一前沿交叉领域未来的发展趋势。

Application of Mass Spectrometry in Research On the Interactions of Anticancer Metallodrugs with Proteins

Investigating the interactions of anticancer metallodrugs with proteins, as well as their effects on the process of drug transport, cellular uptake, metabolism and bioavailability, is very important for structure-based design, improvement of activity and reduction of side effects of anticancer metallodrugs. The soft ionization mass spectrometry including ESI and MALDI can greatly preserve the coordination of drug molecules to biomolecules during the performance, and provide direct information on the binding sites of metallodrugs on proteins. Additionally, mass spectrometry has many advantages such as high sensitivity, low sample consumption, speed, suitable for complex biological samples and so on. Thus, it has become the most powerful tool for studying the interactions of anticancer metallodrugs with proteins. The increasing researches on this field provide not only valuable chemical and biological information for drug discovery, but also greatly promote mass spectrometry itself. Bases on the update progress of our own group on the interactomic studies of anticancer metallodrugs, we presents a review of the latest achievements of research on the interactions of platinum and ruthenium-based anticancer drugs (or candidates) with proteins using bottom-up and top-down mass spectrometric approaches. A brief analysis on the possible future research trends and development in this area is also given.