Sequence-selective metal ion binding to DNA oligomers

Sequence-selective interactions between DNA oligonucleotides and Pt(II) and Pd(II) complexes have been studied by 1D and 2D NMR spectroscopy. Titration of DNA oligomers with diamagnetic metal ion complexes induces chemical shifts of proton resonances close to the site of interaction. Conformational changes in the helical structure were monitored by measuring cross-peak intensities in 2D NOESY maps. Two duplex deoxynucleotides were studied, [d(CGCGCG)]2 and [d(CGCGAATTCGCG)]2, respectively. The hexamer was titrated in the duplex form with cis-[Pt(NH3)2Cl2]2+ (cis-DDP or cisplatin). The dodecamer was titrated with NO(3-)-salts of Pd(aq)2+, [Pd(en)(H2O)2]2+ and [Pd(dien)(H2O)]+, respectively. The reaction between cis-DDP and the hexamer at conditions where the duplex form is retained proceeded exceedingly slowly. In the initial phase of the titration the NOESY map indicates conformational changes induced by noncovalent adduct formation between the intact hexamer and cis-DDP. The more reactive Pd compounds show a tendency towards sequence-selective binding to the duplex dodecamer. The 'naked' Pd ion is very reactive and exhibits selectivity towards the thymine T8 imino proton and N7 on G4. At a Pd(II)/dodecamer ratio of 4:1 the metal ions induce helix-->coil transition. The mono- and bifunctional Pd complexes with 'bulky' ligands attack the dodecamer at the terminal GC base pairs, leaving the central Watson-Crick base pairs intact.