Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, China.
Molecules. 2019 Feb 6;24(3):581. doi: 10.3390/molecules24030581.
The discovery of the anticancer activity of cisplatin and its clinical application has opened a new field for studying metal-coordinated anticancer drugs. Metal-based anticancer drugs, such as cisplatin, can be transported to cells after entering into the human body and form metal⁻DNA or metal⁻protein adducts. Then, responding proteins will recognize adducts and form stable complexes. The proteins that were binding with metal-based anticancer drugs were relevant to their mechanism of action. Herein, investigation of the recognition between metal-based anticancer drugs and its binding partners will further our understanding about the pharmacology of cytotoxic anticancer drugs and help optimize the structure of anticancer drugs. The "soft" ionization mass spectrometric methods have many advantages such as high sensitivity and low sample consumption, which are suitable for the analyses of complex biological samples. Thus, MS has become a powerful tool for the identification of proteins binding or responding to metal-based anticancer drugs. In this review, we focused on the mass spectrometry-based quantitative strategy for the identification of proteins specifically responding or binding to metal-based anticancer drugs, ultimately elucidating their mechanism of action.
顺铂的抗癌活性及其临床应用的发现为研究金属配位抗癌药物开辟了新的领域。铂类抗癌药物进入人体后可被转运到细胞内，并形成金属-DNA 或金属-蛋白质加合物。然后，响应蛋白将识别加合物并形成稳定的复合物。与金属抗癌药物结合的蛋白质与它们的作用机制有关。因此，研究金属抗癌药物与其结合伙伴之间的识别将有助于我们进一步了解细胞毒性抗癌药物的药理学，并有助于优化抗癌药物的结构。“软”电离质谱方法具有灵敏度高、样品消耗低等优点，适用于复杂生物样品的分析。因此，MS 已成为鉴定与金属抗癌药物结合或响应的蛋白质的有力工具。在本文中，我们重点介绍了基于质谱的定量策略，用于鉴定特异性响应或与金属抗癌药物结合的蛋白质，最终阐明其作用机制。
