Ruthenium versus platinum: interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry
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 and compared with that of 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 were found to be similar for all the metallodrugs studied, irrespective of the sequence of the oligonucleotide. A strong preference for guanine residues was established.
Keywords: Ruthenium ; Platinum ; Anticancer ; Oligonucleotides ; Mass spectrometry ; Double-Stranded Dna ; Assisted-Laser-Desorption/Ionization ; In-Vitro ; Pta Complexes ; Cross-Links ; Drugs ; Binding ; Chemotherapy ; Cisplatin ; Adducts
Record created on 2010-06-07, modified on 2016-08-08