Investigation of the binding site of ruthenium complexes to short single-stranded oligodeoxynucleotides using...

In order to elucidate the nature of the interaction between metal complexes and DNA, use was made of short telomere single-stranded oligodeoxynucleotide (ODN) strand 5'-T₁ T₂ A₃ G₄ G₅ G₆ -3' (1) and strands 5'-T₁ C₂ A₃ G₄ G₅ G₆ -3' (2), 5'-T₁ T₂ A₃ C₄ G₅ G₆ -3' (3) and 5'-T₁ C₂ C₃ C₄ C₅ G₆ -3' (4) for the verification of the binding site with four different ruthenium complexes as possible anticancer drug candidates.

The ability to form adducts between ruthenium complexes with short single-stranded 6-mers was investigated through the use of electrospray ionization mass spectrometry (ESI-MS). Full scan ESI mass spectra and collision-induced dissociation (CID) mass spectra were recorded on a high-resolution quadrupole time-of-flight mass spectrometer. The elemental compositions of the adducts and the most important product ions were calculated by exact mass measurements.

ESI-MS measurements showed that the mono-ruthenated ODNs were the main products produced under the conditions for the four ruthenium complexes and each of the ODNs. The CID results revealed that thymine and guanine are the preferred binding sites depending on the different compositions in the ODNs. However, for the ODN of the type: 5'-T₁ C₂ C₃ C₄ C₅ G₆ -3' the coordination site on cytosine was observed as well. The different ruthenium complexes interacted in the same way.

This study showed that the characterization of new ruthenium complexes with short single-stranded telomeric DNA (TTAGGG) and further different ODNs is possible with positive ESI-MS/MS measurement. The identification of thymine and cytosine besides guanine as possible binding sites suggests that the interaction site is highly affected by the ODN's structure.