The anti Z-DNA reactivity of Z-DNA forming sequences is affected by platinum antitumor drugs.
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.
Pérez-Martín
J M
JM
Centro de Biología Molecular CSIC, Universidad Autónoma de Madrid, Facultad de Ciencias, Spain.
Requena
J M
JM
Craciunescu
D
D
López
M C
MC
Alonso
C
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010957:Plasmids
D000970:Antineoplastic Agents; D009838:Oligodeoxyribonucleotides; D009944:Organoplatinum Compounds; C057919:platinum(II) pentamidine; D010419:Pentamidine; D004247:DNA; D002945:Cisplatin