Kinetics of Changes in the Secondary Structure of DNA Induced by the Binding of Platinum Cytostatics

Abstract

It is well established now that the reaction of the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP) with DNA is a complex process. As the primary step cis-DDP binds monofunctionally and only in a secondary reaction the bifunctional binding takes place resulting in the formation of intra- and interstrand cross-links |1–7|. Whereas there is no doubt that the monofunctional binding occurs predominantly at N-7 sites of guanine residues, there is less agreement about the nature of the adducts resulting from the bifunctional interaction |1–5|. It has been concluded that the intrastrand cross-linking is a more frequent event involving mainly two guanines and, to a lesser extent, guanine and adenine, whereas the interstrand cross-linking represents less than 1% of total platinations |3|. Kinetic studies revealed that bifunctional binding to two guanine residues occurred more rapidly than binding to guanine and adenine |1,2|.