DNA-binding properties of antitumor-active cis-bis(pyridine)platinum(II) organoamides

Abstract

 The interaction of the new antitumor-active platinum organoamide complexes [Pt{N(p–HC₆F₄)CH₂}₂(py)₂] and [Pt{N(C₆F₅)CH₂}₂(py)₂] (py = pyridine) with small G-containing (oligo)nucleotides [GMP, d(GpG)] has been studied to establish whether or not these compounds can bind to DNA in an analogous manner to cisplatin. The reaction products have been analyzed by ¹H, ¹⁹F and ³¹P NMR spectroscopy. From the NMR data it is concluded that the {Pt(py)₂}²⁺ moiety binds to the N7 position of the G base, analogously to cisplatin, with the organoamide ligand acting as the leaving group. For the GG-N7,N7 adduct, structural differences are found for the sugar conformation, compared with cisplatin. These differences may account for the activity of these new compounds in tumor cell lines resistant to cisplatin.