| Abstract
| - Intrinsic and acquired resistance are major drawbacks of platinum-based cancer therapy. The proteinsuperfamily of cysteine- and ZnII-rich proteins, metallothioneins (MT), efficiently inactivate these antitumordrugs because of the strong reactivity of platinum compounds with S-donor molecules. In this study thereactions of human Zn7MT-2 with twelve cis/trans-[Pt(N-donor)2Cl2] compounds and [Pt(dien)Cl]Cl, includingnew generation drugs, were investigated and the products characterized. A comparison of reaction kineticsrevealed that trans-PtII compounds react faster with Zn7MT-2 than cis-PtII compounds. The characterizationof the products showed that while all ligands in cis-PtII compounds were replaced by cysteine thiolates,trans-PtII compounds retained their N-donor ligands, thus remaining in a potentially active form. Theseresults provide an increased understanding of the role of MT in the acquired resistance to platinum-basedanticancer drugs.
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