Cytotoxicity studies of [PtCl 2(H 2bim)] (H 2bim = 2,2′-biimidazole): Study of its interaction with a small protein PCI (potato carboxypeptidase inhibitor)

Abstract

The effect of the platinum compound [PtCl 2(H 2bim)] (H 2bim = 2,2′-biimidazole) on the plasmid DNA conformation was previously studied by electrophoresis in agarose gel and on calf thymus DNA by circular dichroism spectroscopy. The effect of this compound on pBR322 plasmid DNA has now been visualized by atomic force microscopy, which shows that the complex modifies the DNA in the same way as cisplatin does. The cytotoxic activity of [PtCl 2(H 2bim)] in HeLa-229, HL-60, A2780 and A2780cisR cell lines has also been evaluated. Likewise, the interaction of [PtCl 2(H 2bim)] with the small protein potato carboxypeptidase inhibitor (PCI) and a PCI mutant in which glycine 39 was substituted by methionine has been followed by HPLC/mass spectrometry. The interaction with the mutant protein PCI showed the formation of monofunctional adducts that ultimately gave bifunctional adducts. PCI mutant protein could be a good carrier of this platinum compound to the tumour cells in which the antiproliferative behaviour was demonstrated.