Viscosity, nicking, thermal and alkaline denaturation studies on three classes of DNA-platinum complex

Viscosity, nicking, thermal denaturation and alkaline denaturation studies were used to investigate perturbations induced in the DNA secondary structure after complexation with platinum compounds. Three types of DNA-platinum complex, representative of the different modes of platinum binding, have been studied. Cis-Pt(NH3)2Cl2, which forms a cis-bidentate complex with DNA, strongly decreased the viscosity and, according to thermal and alkaline denaturations, destabilized the macromolecule. On the contrary, trans-Pt(NH3)2Cl2, a trans-bidentate complex, stabilized the DNA secondary structure and decreased the viscosity but much less than did cis-Pt(NH3)2Cl2. [Pt(dien)Cl]Cl, a monodentate complex, had no effect on the viscosity; however, addition of this compound stabilized DNA up to 0.01 platinum bound per nucleotide while further Pt binding destabilized the macromolecule. Cis- and trans-Pt(NH3)2Cl2 renatured thermally denatured DNA, which has been interpreted as evidence for the presence of interstrand crosslinks. [Pt(dien)Cl]Cl, on the other hand, did not renature DNA. If the renaturation observed for the bidentate compounds is due only to the presence of interstrand crosslinks, then one interstrand crosslink is found when 400-1000 molecules of the platinum isomer are bound per T7 DNA molecule. Electron microscopy results show that the three types of DNA-platinum complex do not nick DNA up to 0.01 bound platinum per nucleotide.