Investigation on the Interactions of NiCR and NiCR-2H with DNA

Abstract EN

We report here a biophysical and biochemical approach to determine the differences in interactions of NiCR and NiCR-2H with DNA.

Our goal is to determine whether such interactions are responsible for the recently observed differences in their cytotoxicity toward MCF-7 cancer cells.

Viscosity measurement and fluorescence displacement titration indicated that both NiCR and NiCR-2H bind weakly to duplex DNA in the grooves.

The coordination of NiCR-2H with the N-7 of 2′-deoxyguanosine 5′-monophosphate (5′-dGMP) is stronger than that of NiCR as determined by H1 NMR.

NiCR-2H, like NiCR, can selectively oxidize guanines present in distinctive DNA structures (e.g., bulges), and notably, NiCR-2H oxidizes guanines more efficiently than NiCR.

In addition, UV and H1 NMR studies revealed that NiCR is oxidized into NiCR-2H in the presence of KHSO5 at low molar ratios with respect to NiCR (≤4).