UNWINDING OF SUPERCOILED DNA BY PLATINUM ETHIDIUM AND RELATED COMPLEXES

A gel electrophoretic mobility shift assay has been used to determine the unwinding of closed circular, supercoiled pUC 19 plasmid DNA induced by a variety of platinum complexes that differ in their coordination mode to the double helix. Included are the anticancer drug cisplatin and several of its analogues, compounds in which the organic intercalator ethidium is coordinated to platinum through an exocyclic amino group, and molecules in which two platinum centers are tethered by a polymethylene chain. The unwinding angles (phi) for the 12 compounds investigated range from 6-degrees to 19-degrees, with phi increasing in the order monofunctional binding < bifunctional binding < monofunctional plus intercalative binding < bifunctional plus intercalative binding. Unwinding titration experiments thus provide a useful screen of the binding mode of divalent platinum complexes that modify DNA. In the case of the platinum-ethidium complexes, the phi-values provide experimental evidence for both covalent and intercalative binding of this interesting class of compounds. Information of this kind might facilitate the design of compounds, including antitumor drug candidates, that unwind DNA to any desired extent.