Merlino Antonello, Marzo Tiziano, Messori Luigi
Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126, Napoli, Italy) and CNR Institute of Biostructure and Bioimages, Via Mezzocannone 16, 80100, Napoli (Italy.
Department of Chemistry and Industrial Chemistry, University of Pisa, via Moruzzi, 13, 56124, Pisa, Italy.
Chemistry. 2017 May 23;23(29):6942-6947. doi: 10.1002/chem.201605801. Epub 2017 Feb 14.
Interactions of metal-based drugs with proteins and consequent adduct formation (the so-called "protein metalation" process) play a key role in the mode of action of several anticancer agents and in determining their toxicological profile. Through a novel investigative strategy grounded on the combined use of electrospray ionization mass spectrometry (ESI MS) and biological macromolecule X-ray crystallography we show that it is possible to clarify in depth the metalation process of small model proteins; a number of instructive examples are provided. Recently, this kind of investigative approach has been extended to bigger proteins such as human serum albumin and horse spleen ferritin, with rather encouraging results. Overall, by application of this strategy, metalation of proteins caused by anticancer metallodrugs can be disclosed in the molecular detail.
金属基药物与蛋白质的相互作用以及随之而来的加合物形成（即所谓的“蛋白质金属化”过程）在几种抗癌药物的作用模式以及确定其毒理学特征方面起着关键作用。通过基于电喷雾电离质谱（ESI MS）和生物大分子X射线晶体学联合使用的新型研究策略，我们表明可以深入阐明小模型蛋白质的金属化过程；提供了许多有启发性的例子。最近，这种研究方法已扩展到更大的蛋白质，如人血清白蛋白和马脾铁蛋白，取得了相当令人鼓舞的结果。总体而言，通过应用这种策略，可以在分子细节上揭示抗癌金属药物引起的蛋白质金属化。
