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Nucleic Acids Research, 1992, Vol. 20, No. 7 1697-1703
© 1992

CHEMISTRY

B{uparrow} Z DNA conformational changes induced by a family of dinuclear bis(platinum) complexes

Andrew Johnson, Yun Qu1, Bennett Van Houten and Nicholas Farrell1,*

Departments of Pathology, University of Vermont Burlington, VT 05405, USA 1Chemistry and The Vermont Cancer Center, University of Vermont Burlington, VT 05405, USA

*To whom correspondence should be addressed

Received December 2, 1991. Revised January 31, 1992. Accepted January 31, 1992.

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{uparrow}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{uparrow}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 mono-meric agents such as [Co(NH3)6]3+. The possible biological consequences of the Z-DNA induction by bis(platlnum) complexes are discussed.


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[Abstract] [Full Text]


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