The berenil ligand directs the DNA binding of the cytotoxic drug Pt-berenil

To determine the affinity towards DNA sequences of novel antitumor drags in comparison with their parental compounds may lead to the design of new analogous drags with improved antitumor activity. Thus, the affinities of Pt-berenil towards different DNA sites relative to cis-DDP and berenil drags were analysed using DNase I footprinting and restriction endonuclease analysis. The data show that the Pt-berenil drag inhibits the cutting activity of Hind III enzyme to the same extent as the berenil ligand. In contrast, inhibition by Pt-berenil of the cutting activity of Bam III enzyme is significantly lower than that of cis-DDP. These results indicate that although the cis-Pt(II) centres of Pt-berenil maintain certain affinity toward G + C regions, which rare the main binding sequences of cis-DDP, however, the berenil ligand seems to direct the Pt-berenil molecule towards A + T regions, which are the binding sequences preferred by berenil. In fact, H-1- and Pt-195-NMR spectra of Pt-berenil:nucleoside complexes show that Pt-berenil not only covalently binds to N7 of guanosine bat also to N1/N7 of adenosine. (C) 1997 Elsevier Science Inc.