Ruthenium versus Platinum: Interactions of Anticancer Metallodrugs with Duplex Oligonucleotides Characterised by Electrospray Ionisation-Mass Spectrometry

Abstract

The binding of the ruthenium-based anticancer drug candidates KP1019, NAMI-A, and RAPTA-T towards different double-stranded oligonucleotides was probed by electrospray ionisation-mass spectrometry (ESI-MS) and compared to the widely used platinum-based chemotherapeutics cisplatin, carboplatin and oxaliplatin. It was found that the extent of adduct formation decreased in the following order: cisplatin > oxaliplatin > NAMI-A > RAPTA-T > carboplatin > KP1019. In addition to the characterisation of the adducts formed with the DNA models, the binding sites of the metallodrugs on the oligonucleotides were elucidated employing top-down tandem mass spectrometry and found to be similar for all the metallodrugs studied, irrespective of the sequence of the oligonucleotide. A strong preference for guanine residues was established.