Casini Angela, Guerri Annalisa, Gabbiani Chiara, Messori Luigi
Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze, Italy.
J Inorg Biochem. 2008 May-Jun;102(5-6):995-1006. doi: 10.1016/j.jinorgbio.2007.12.022. Epub 2008 Jan 8.
There is considerable interest today for the reactions of anticancer metallodrugs with proteins as these interactions might feature processes that are crucial for the biodistribution, the toxicity and even the mechanism of action of this important group of anticancer agents. We survey here the results of research activities carried out in our "Laboratory of Metals in Medicine" (Department of Chemistry, University of Florence) during the last three years, concerning the molecular characterisation of adducts formed between platinum, ruthenium and gold metallodrugs and a few model proteins. Valuable structural and functional information on these adducts could be derived from several biophysical studies mainly relying on the application of X-ray diffraction and ESI MS techniques. The value and the limitations of both approaches are outlined through a number of examples. Remarkably, the structural and functional information achieved on the respective metallodrug-protein adducts allowed us to identify some general trends in the reactivity of anticancer metallodrugs with protein targets.
如今，人们对抗癌金属药物与蛋白质的反应极为关注，因为这些相互作用可能涉及对这类重要抗癌药物的生物分布、毒性乃至作用机制至关重要的过程。在此，我们概述了过去三年在我们（佛罗伦萨大学化学系“医学金属实验室”）开展的研究活动结果，这些研究涉及铂、钌和金金属药物与一些模型蛋白质形成的加合物的分子表征。关于这些加合物的有价值的结构和功能信息可从一些主要依靠X射线衍射和电喷雾质谱技术应用的生物物理研究中获得。通过多个实例概述了这两种方法的价值和局限性。值得注意的是，在相应的金属药物 - 蛋白质加合物上获得的结构和功能信息使我们能够确定抗癌金属药物与蛋白质靶点反应性的一些一般趋势。
