Reactivity of transplatin-modified oligonucleotides in triple-helical DNA complexes

The purpose of this work was to gain insight into the formation of interstr and cross-links in DNA triple helices resulting from the association betwee n double-stranded DNAs and the complementary oligonucleotides containing a single transplatin monofunctional adduct either trans-[Pt(NH3)(2)(dG)Cl](+) or trans-[Pt(NH3)(2)(dC)Cl](+). Depending upon its location along the olig onucleotide, a platinated guanine residue increases or decreases the therma l stability of the platinated triplexes, as shown on model systems in which the transplatin monofunctional adduct was replaced by a diethylenetriamine platinum(II) adduct. The interstrand cross-linking reaction has been studie d in triplexes containing a single transplatin monofunctional adduct as a f unction of several parameters. The rate of closure of the monofunctional ad duct into an interstrand cross-link depends upon the nature of the adduct b ut not strongly on its location along the Hoogsteen strand. The closure of trans-[Pt(NH3)(2)(dC)Cl](+) is faster than that of trans-[Pt(NH3)(2)(dG)Cl] (+). Whereas the closure of trans-[Pt(NH3)(2)(dC)Cl](+) is hardly affected by the presence of a high concentration of NaCl in the medium, the closure of trans-[Pt(NH3)(2)(dG)Cl](+) is largely slowed down. These results are di scussed in the context of the potential use of the platinated oligonucleoti des to modulate gene expression.