DNA interactions of antitumor cisplatin analogs containing enantiomeric amine ligands

Modifications of natural DNA and synthetic oligodeoxyribonucleotide duplexe s in a cell-free medium by analogs of antitumor cisplatin containing enanti omeric amine ligands, such as cis-[PtCl2(RR-DaB)] and cis-[PtCl2(RR-DAB)] ( DAB = 2,3-diaminobutane), were studied by various methods of molecular biop hysics and biophysical chemistry. These methods include DNA binding studies by pulse polarography and atomic absorption spectrophotometry, mapping of DNA adducts using transcription assay, interstrand cross-linking assay usin g gel electrophoresis under denaturing conditions, differential scanning ca lorimetry, chemical probing, and bending and unwinding studies of the duple xes containing single. site-specific cross-link. The major differences resu lting from the modification of DNA by the two enantiomers are the thermodyn amical destabilization and conformational distortions induced in DNA by the 1,2-d(GpG) intrastrand cross-link. It has been suggested that these differ ences are associated with a different biological activity of the two enanti omers observed previously. In addition, the results of the present work are also consistent with the view that formation of hydrogen bonds between the carbonyl oxygen of the guanine residues and the "quasi equatorial" hydroge n of the cia amine in the 1,2-d(GpG) intrastrand cross-link plays an import ant role in determining the character of the distortion induced in DNA by t his lesion.