Modifications of the DNA secondary structure upon platinum binding: a proposed model

Abstract

A number of physico-chemical techniques were used to study the interaction between a series of platinum compounds and DNA. Spectrofluorometry, ultraviolet spectroscopy (UV), circular dichroism (CD), melting curves, kinetics and electron microscopy (EM) were found powerful in the differentiation of the DNA secondary structure modifications upon platinum binding. Three types of alterations are clearly shown and can be correlated with the mode of platinum binding to DNA. Type I is typical of a cis attack, type II of a trans attack and type III, of a monofunctional platinum binding. In type III, no significant DNA modifications were noticed in UV, CD, fluorescence and EM. The different results obtained with cis and trans platinum compounds indicate a strong perturbation of the DNA structure upon bidentate platinum binding. These two types of compounds were found to shorten the DNA length as shown in EM. A correlation was found between the kinetics of the DNA-Platinum interaction for a series of cis-compounds and their activity on leukemia L1210 in mice. A model for the cis-Pt(NH3)2Cl2 interaction with DNA will be discussed.