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-P tCl2)(3) (pentamidine)(3)][PtCl4](2) and cis-DDP [cis-diamminedichloro platimum(II)] to pUC8 DNA, as well as the effect of the binding of the se platinum compounds on the cutting effectiveness of Bam HI, Hind III , and Sal I restriction endonucleases, were determined by flameless at omic absorption spectroscopy and gel electrophoresis, respectively. Th e results show that covalent DNA platination is 12% to 22% lower in DN A:Pt-pentamidine complexes than in DNA:cis-DDP at the same molar rate of platinum/nucleotide, and the number of Pt-pentamidine molecules bou nd to DNA is significantly lower in Pt-pentamidine:DNA complexes than in cis-DDP:DNA complexes. Although both compounds inhibit Bam HI cleav age of pUC8 DNA, Pt-pentamidine does not prevent the cutting activity of Hind III, in contrast with cis-DDP, Neither cis-DDP nor Pt-pentamid ine inhibits the cutting activity of Sal I, whose recognition sequence neighbors the Bam HI and Hind III sites.