The anti Z-DNA reactivity of Z-DNA forming sequences is affected by platinum antitumor drugs.

Abstract The effect of binding of platinum antitumor drugs, cis-diamminedichloroplatinum (II) (cis-DDP) and Pt-pentamidine, on the Z-DNA reactivity of potential Z-DNA forming sequences has been studied by enzyme-linked immunosorbent assay. The results indicate that cis-DDP and Pt-pentamidine increase the Z-DNA reactivity of plasmids containing a (dG-dC)16 insert (pUCZ8) and a native Z-DNA forming sequence of Drosophila hydei (pF18). The molar ratio of platinum bound to nucleotides (rb) to produce 50% of Z-DNA reactivity was 0.10 for cis-DDP:pF18, 0.15 for Pt-pentamidine:pF18, and 0.10 for cis-DDP:pUCZ8 and Pt-pentamidine:pUCZ8. The efficacy of Pt-pentamidine to provoke Z-DNA reactivity is 2.5-fold higher than that of cis-DDP. While Pt-pentamidine was capable of inducing Z-DNA reactivity in a GC-rich DNA sequence of the hsp 70 protein of Trypanosoma cruzi (p2M4EO3) and in sequences of pUC8, cis-DDP suppresses Z-DNA reactivity. CD spectra of poly(dG-me5dC).poly(dG-me5dC) modified by the drugs suggest that the increase in Z-DNA reactivity observed in plasmids upon drug binding may be due to shifting towards Z-DNA or a Z-DNA like conformation.