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

The purpose of this work was to gain insight into the formation of interstrand cross-links in DNA triple helices resulting from the association between 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 oligonucleotide, a platinated guanine residue increases or decreases the thermal stability of the platinated triplexes, as shown on model systems in which the transplatin monofunctional adduct was replaced by a diethylenetriamineplatinum(II) adduct. The interstrand cross-linking reaction has been studied in triplexes containing a single transplatin monofunctional adduct as a function of several parameters. The rate of closure of the monofunctional adduct into an interstrand cross-link depends upon the nature of the adduct but 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 discussed in the context of the potential use of the platinated oligonucleotides to modulate gene expression.