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)nNH2)]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)nNH2)]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.
Wu
P K
PK
College of Medicine, University of Vermont, Burlington, USA.
Kharatishvili
M
M
Qu
Y
Y
Farrell
N
N
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry; D004996:Ethidium / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D015394:Molecular Structure; D009690:Nucleic Acid Conformation / Q000187:drug effects; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D013053:Spectrophotometry
D018736:DNA Adducts; D017671:Platinum Compounds; D004247:DNA; D004996:Ethidium