B----Z DNA conformational changes induced by a family of dinuclear bis(platinum) complexes.
The reactions of bis(platinum) complexes of general formula [(PtClm(NH3)3-m)2(NH2(CH2)nNH2)]2(2-m)+ were studied with poly(dG-dC).poly(dG-dC), poly(dG-m5dC).poly(dG-m5dC) and poly(dG).poly(dC). When m = 0 (Complexes II, n = 2,4) the complexes are saturated 4+ cations capable only of electrostatic interactions with the polynucleotide. Where m = 1 the complexes contain two monodentate platinum coordination spheres with the chloride trans to the diamine bridge (Complexes I, n = 2,4, 1,1/t,t). Complexes I give CD spectra characteristic of a 'Z-like' conformation upon reaction with poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) but not poly(dG).poly(dC). The B----Z transition appears independent of interplatinum diamine chain length. As little as 1 bis(platinum) complex per 25-30 base pairs is sufficient to observe the Z-like spectrum. Covalent binding is however not a prerequisite for Z-DNA formation because the polyvalent cations II are also very effective in inducing the B----Z transition in either poly(dG-dC).poly(dG-dC) or poly (dG-m5dC).poly(dG-m5dC). In these cases, the concentrations of II required are significantly lower than analogous monomeric agents such as [Co(NH3)6]3+. The possible biological consequences of the Z-DNA induction by bis(platinum) complexes are discussed.
Johnson
A
A
Department of Pathology, University of Vermont, Burlington 05405.
Qu
Y
Y
Van Houten
B
B
Farrell
N
N
D002942:Circular Dichroism; D002945:Cisplatin / Q000378:metabolism*; D004247:DNA / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011066:Poly C / Q000378:metabolism; D011068:Poly G / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000378:metabolism*; D013054:Spectrophotometry, Atomic
D011089:Polydeoxyribonucleotides; D011068:Poly G; C023826:poly(dC); C026628:poly(dG); C019530:poly(dC-dG); D011066:Poly C; D004247:DNA; D002945:Cisplatin