Marasco Daniela, Messori Luigi, Marzo Tiziano, Merlino Antonello
Department of Pharmacy, University of Naples Federico II, via Montesano 12, 80120, Napoli, Italy.
Dalton Trans. 2015 Jun 14;44(22):10392-8. doi: 10.1039/c5dt01279a.
The model protein hen egg white lysozyme was challenged with oxaliplatin and cisplatin. ESI mass spectrometry, surface plasmon resonance and thermal shift analyses demonstrate the formation of a bis-platinum adduct, though in very small amounts. Crystals of the bis-platinum adduct were obtained using two different preparations and the X-ray structures were solved at 1.85 Å and 1.95 Å resolution. Overall, the obtained data point out that, under the analyzed conditions, the two Pt drugs have similar affinities for the protein, but bind on its surface at two non-overlapping sites. In other words, these two drugs manifest a significantly different reactivity with this model protein and do not compete for the same protein binding sites.
用奥沙利铂和顺铂对模型蛋白鸡蛋清溶菌酶进行处理。电喷雾电离质谱、表面等离子体共振和热迁移分析表明形成了双铂加合物,尽管量非常少。使用两种不同的制剂获得了双铂加合物的晶体,并在1.85 Å和1.95 Å分辨率下解析了X射线结构。总体而言,所获得的数据表明,在分析的条件下,这两种铂类药物对该蛋白具有相似的亲和力,但在其表面的两个不重叠位点结合。换句话说,这两种药物与该模型蛋白表现出明显不同的反应性,并且不会竞争相同的蛋白结合位点。