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.
Groessl
Michael
M
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, Switzerland. michael.groessl@epfl.ch
Tsybin
Yury O
YO
Hartinger
Christian G
CG
Keppler
Bernhard K
BK
Dyson
Paul J
PJ
D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
D000970:Antineoplastic Agents; D009841:Oligonucleotides; D009942:Organometallic Compounds; D010984:Platinum; D012428:Ruthenium