THE INTERACTION OF PLATINUM COMPLEXES WITH DNA STUDIED BY DIFFERENTIAL SCANNING CALORIMETRY

Abstract

Differential scanning calorimetry (DSC) was used to study the interaction of platinum complexes with the linearized plasmid pJL3-TB5 DNA. An effective antitumor drug, cis-dichlorodiammineplatinum(II) (cis-DDP), caused the positions of DSC peaks to shift to a lower temperature range, showing that the heat stability of DNA decreases due to the adduct formed by the cis-DDP; the antitumor-inactive geometrical isomer trans dichlorodiammineplatinum(II) (trans-DDP) caused a larger variation in the melting profile than cis-DDP did. With another antitumor platinum complex, 1, 2-cyclohexanediamine(dach)platinum chloride (PtCl₂(dach)), a complex with higher antitumor activity, the effect on the melting profile was smaller than that of others with less antitumor activity. These results show that the antitumor activity of platinum complexes is inversely proportional to their ability to disrupt DNA structure.