Modification of the recognition of restriction sites of plasmid DNA by the antitumor drug Pt-pentamidine.

The rate of binding of the antineoplastic drugs Pt-pentamidine [(cis-PtCl2)3(pentamidine)3][PtCl4]2 and cis-DDP [cis-diamminedichloroplatimum(II)] to pUC8 DNA, as well as the effect of the binding of these platinum compounds on the cutting effectiveness of Bam HI, Hind III, and Sal I restriction endonucleases, were determined by flameless atomic absorption spectroscopy and gel electrophoresis, respectively. The results show that covalent DNA platination is 12% to 22% lower in DNA: Pt-pentamidine complexes than in DNA: cis-DDP at the same molar rate of platinum/nucleotide, and the number of Pt-pentamidine molecules bound to DNA is significantly lower in Pt-pentamidine: DNA complexes than in cis-DDP: DNA complexes. Although both compounds inhibit Bam HI cleavage of pUC8 DNA, Pt-pentamidine does not prevent the cutting activity of Hind III, in contrast with cis-DDP. Neither cis-DDP nor Pt-pentamidine inhibits the cutting activity of Sal I, whose recognition sequence neighbors the Bam HI and Hind III sites.