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

Abstract

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(NH 3) 3} 2(H 2N(CH 2) nNH 2)] 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(NH 3) 2} 2(H 2N(CH 2) nNH 2)] 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.