Ruthenium versus platinum: Interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry

Author(s)
Michael Groessl, Yury O. Tsybin, Christian Hartinger, Bernhard Keppler, Paul J. Dyson
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 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.

Organisation(s)
Department of Inorganic Chemistry
External organisation(s)
École polytechnique fédérale de Lausanne
Journal
Journal of Biological Inorganic Chemistry
Volume
15
Pages
677-688
No. of pages
12
ISSN
0949-8257
DOI
https://doi.org/10.1007/s00775-010-0635-0
Publication date
2010
Peer reviewed
Yes
Austrian Fields of Science 2012
104003 Inorganic chemistry, 1030 Physics, Astronomy, 301303 Medical biochemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/7ff77084-87c4-4a8b-b5d7-486eccc18c5c