A circular dichroism study of ethidium bromide binding to Z-DNA induced by dinuclear platinum complexes

Dinuclear bis(platinum) complexes have been shown previously to induce the B --> Z transition in synthetic DNAs (Nucleic Acids Res. 7, 1697-1703; J. Inorganic Biochem. 54, 207-220). In this paper, the reversibility of the Z conformation back to the B form was assessed by treatment of the induced Z form in poly(dG-dC).poly(dG-dC) with ethidium bromide (Etd). Z-DNA induced by the tetra-amine cations [{Pt(NH3)(3)}(2)(H2N(CH2)(n)NH2)](4+), which are capable of only electrostatic interactions with the polynucleotide, was readily reversible. The spectroscopic data mirrored that of ethidium bromide/poly(dG-dC).poly(dG-dC) in the presence of 4.4 M NaCl. In contrast, Z-DNA induced by the bifunctional complexes [{trans-PtCl(NH3)(2)}(2)(H2N(CH2)(n)NH2)](2+) did not produce spectra typical of Etd intercalation and reversal to B-form DNA. The original Z-form CD spectra of DNA treated with the bifunctional complexes could be reobtained following removal of Etd by extensive dialysis. The bifunctional complexes are very effective interstrand cross-linking agents. The data suggest that interstrand cross-linking by dinuclear complexes can stabilize or ''lock'' the Z-conformation prohibiting its reversal to the B-form. The implications for the biological activity of the dinuclear complexes are briefly discussed.