Interactions between human copper chaperone Atox1 and cisplatin, carboplatin, nedaplatin and oxaliplatin studied by ESI mass spectrometry

摘要

Increasing evidence indicates that the copper chaperone Atox1 involves the mechanism of Pt-drugs. Here, the interactions of Atox1 with cisplatin and cisplatin analogues were studied. Results show that, like cisplatin, the other three Pt complexes can interact with Atox1 and Cu-I coordination obviously enhances the platination of Atox1. Cisplatin, carboplatin and nedaplatin formed some of adducts with the same composition due to having the same cis-diammine carrier ligands and differ only in the leaving groups. Nedaplatin, similar to carboplatin, was relatively inert with respect to cisplatin. Remarkably, an unexpected adduct with loss' of the 1, 2-diaminocyclohexane (DACH) carrier ligand were observed in the reaction of oxaliplatin with holo-Atox1. These results indicate that both platination adducts and rates of platination are significantly influenced by the ligand and cuprous ion, suggesting the probably different influence of Atox1 on Pt-drugs in vivo. (C) 2017 Elsevier B.V. All rights reserved.