DNA-BINDING PROPERTIES OF ANTITUMOR-ACTIVE CIS-BIS(PYRIDINE)PLATINUM(II) ORGANOAMIDES

The interaction of the new antitumor-active platinum organoamide compl exes [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 H-1, F-19 and P-31 NMR spectroscopy. From the NMR da ta it is concluded that the {Pt(py)(2)}(2+) moiety binds to the N7 pos ition of the G base, analogously to cisplatin, with the organoamide li gand acting as the leaving group. For the GG-N7,N7 adduct, structural differences are found for the sugar conformation, compared with cispla tin. These differences may account for the activity of these new compo unds in tumor cell lines resistant to cisplatin.