Fulltext

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

Groessl, Michael ; Tsybin, Yury ; Hartinger, Christian ; Keppler, Bernhard ; Dyson, Paul

In: JBIC Journal of Biological Inorganic Chemistry, 2010, vol. 15, no. 5, p. 677-688

Add to personal list
    Title
    • Ruthenium versus platinum: interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry
    Author
    • Groessl, Michael. Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland
    • Tsybin, Yury. Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland
    • Hartinger, Christian. Institute of Inorganic Chemistry, University of Vienna, Währinger Str. 42, 1090, Vienna, Austria
    • Keppler, Bernhard. Institute of Inorganic Chemistry, University of Vienna, Währinger Str. 42, 1090, Vienna, Austria
    • Dyson, Paul. Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • JBIC Journal of Biological Inorganic Chemistry, 2010, vol. 15, no. 5, p. 677-688. Springer-Verlag
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:314110
    Summary
    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