Michael D. Reily

Evidence for similar structural changes on binding of platinum anti‐tumor agents to DNA and nucleosomes

The influence of Pt(II) compounds on the 31P NMR spectra of natural DNA, synthetic polynucleotides, and nucleosomes was investigated. With Pt complexes which are anti‐tumor agents, a new peak or shoulder centered at ~ 1.2 ppm downfield from the untreated DNA signal was observed. When Pt compounds known not to be anti‐tumor agents were studied, no such new signal was observed. The most reasonable explanation for the downfield resonance is that it is a consequence of a structural change induced in the DNA by the anti‐tumor agent. Since the effect of the Pt compounds on nucleosomes was similar, the same structural change is probably occurring in DNA in solution and in nucleosomes. A nonalternating dG · dC polymer, but not alternating G·C or any A·T polymers, exhibited a similar spectral change and this finding suggests that the structural change in the DNA arises primarily from reaction of Pt anti‐tumor agents with adjacent G residues.

Pt-DNA Interactions: Oligonucleotide Models

Modern 2D NMR studies of oligonucleotides can provide insight into unusual structures present in DNA or RNA, such as hairpins, or novel structures formed by the treatment of DNA with anticancer drugs.1–11 Although 1H NMR spectra of regular duplex DNA structures can be assigned with little difficulty with the sequential assignment method, the spectra of conformationally flexible structures may lack some 1H-1H NOE crosspeaks needed for sequential assignments.2,3