The reactivity of the anticancer drug picoplatin (cis-amminedichlorido(2-methylpyridine)platinum(II) complex) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) was investigated by electrospray ionisation mass spectrometry (ESI MS) and X-ray crystallography. The data were compared with those previously obtained for the adducts of these proteins with cisplatin, carboplatin and oxaliplatin under the same experimental conditions. ESI-MS data show binding of Pt to both proteins, with fragments retaining the 2-methylpyridine ligand and, possibly, a chloride ion. X-ray crystallography identifies different binding sites on the two proteins, highlighting a different behaviour of picoplatin in the absence or presence of dimethyl sulfoxide (DMSO). Metal-containing fragments bind to HEWL close to the side chains of His15, Asp18, Asp119 and both Lys1 and Glu7, whereas they bind to RNase A on the side chain of His12, Met29, His48, Asp53, Met79, His105 and His119. The data suggest that the presence of DMSO favours the loss of 2-methylpyridine and alters the ability of the Pt compound to bind to the two proteins. With both proteins, picoplatin appears to behave similarly to cisplatin and carboplatin when dissolved in DMSO, whereas it behaves more like oxaliplatin in the absence of the coordinating solvent. This study provides important insights into the pharmacological profile of picoplatin and supports the conclusion that coordinating solvents should not be used to evaluate the biological activities of Pt-based drugs.

中文翻译：

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吡铂与蛋白质的结合：溶菌酶和核糖核酸酶 A 的加合物的 X 射线结构和质谱数据

通过电喷雾电离质谱（ESI）研究了抗癌药物吡铂（顺式二氯氨（2-甲基吡啶）铂（II）复合物）与模型蛋白鸡蛋清溶菌酶（HEWL）和牛胰腺核糖核酸酶（RNase A）的反应性MS）和 X 射线晶体学。将这些数据与先前在相同实验条件下获得的这些蛋白质与顺铂、卡铂和奥沙利铂的加合物的数据进行比较。 ESI-MS 数据显示 Pt 与两种蛋白质的结合，片段保留了 2-甲基吡啶配体，并且可能还保留了氯离子。 X 射线晶体学鉴定了两种蛋白质上的不同结合位点，突出显示了吡铂在不存在或存在二甲亚砜 (DMSO) 的情况下的不同行为。含金属片段与靠近 His15、Asp18、Asp119 以及 Lys1 和 Glu7 侧链的 HEWL 结合，而与 His12、Met29、His48、Asp53、Met79、His105 和 His119 侧链上的 RNase A 结合。数据表明，DMSO 的存在有利于 2-甲基吡啶的损失，并改变 Pt 化合物与两种蛋白质结合的能力。对于这两种蛋白质，当溶解在 DMSO 中时，吡铂的行为似乎与顺铂和卡铂相似，而在没有配位溶剂的情况下，其行为更像奥沙利铂。这项研究为吡铂的药理学特征提供了重要的见解，并支持了不应使用配位溶剂来评估铂基药物的生物活性的结论。