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金属基药物的蛋白质金属化:X射线晶体学和质谱研究。

Protein metalation by metal-based drugs: X-ray crystallography and mass spectrometry studies.

作者信息

Messori L, Merlino A

机构信息

Department of Chemistry, University of Florence, Italy.

出版信息

Chem Commun (Camb). 2017 Oct 24;53(85):11622-11633. doi: 10.1039/c7cc06442j.

Abstract

The combined use of X-ray crystallography and mass spectrometry represents a valuable strategy to investigate and characterize protein metalation induced by anticancer metal-based drugs. Here, we summarize a series of significant results recently obtained in our laboratories upon the examination of the structures of several adducts of proteins with representative metallodrugs (mostly containing ruthenium, gold and platinum). The general mechanisms of protein metalation that emerge from a careful comparative analysis of these structures are illustrated and their mechanistic implications are discussed. Possible directions for future work in the field are delineated.

摘要

X射线晶体学和质谱联用是研究和表征抗癌金属基药物诱导的蛋白质金属化的一种有价值的策略。在此,我们总结了最近在我们实验室中通过研究几种蛋白质与代表性金属药物(主要含钌、金和铂)的加合物结构而获得的一系列重要结果。阐述了通过对这些结构进行仔细比较分析得出的蛋白质金属化的一般机制,并讨论了其机制意义。还描绘了该领域未来工作的可能方向。

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