Mass spectrometric analysis of ubiquitin-platinum interactions of leading anticancer drugs: MALDI versus ESI
- Author(s)
- Christian Hartinger, Wee Han Ang, Angela Casini, Luigi Messori, Bernhard Keppler, Paul J. Dyson
- Abstract
The protein binding of anticancer metallodrugs is regarded as an important part in their mode of action both for delivering the active moiety into the tumor but also being responsible for deactivation and/or unwanted side effects. Characterization of protein binding and release may allow new drugs to be designed which are devoid of protein interactions or capable of binding selectively to protein targets. Herein, we report the comparison of different ionization techniques, i.e. matrix-assisted laser desorption/ionization (MALDI) and nanoelectrospray ionization mass spectrometry (nESI-MS), for the analysis of small protein-Pt anticancer drug interactions. For this purpose, cisplatin, transplatin and oxaliplatin were incubated with the model protein ubiquitin (Ub) at a molar ratio of 2: 1 (Pt: Ub) followed by MS analysis. Cisplatin, transplatin and oxaliplatin formed mainly monoadducts with Ub, but of significantly different composition. As reported earlier, cisplatin forms mainly bifunctional Ub-[Pt(NH3)2] adducts, while with transplatin the most abundant adduct was found to be a monofunctional Ub-[Pt(NH3)2Cl] species. Oxaliplatin formed exclusively bifunctional species of the formula Ub-[Pt(chxn)] (chxn = cyclohexane-1,2- diamine). The applied analysis methods provide comparable results. However, the higher resolution of the nESI-quadrupole time-of-flight (QToF)-MS allowed unambiguous characterization of a series of mono- and bis-adducts including Ub-[Pt(NH3)2(H2O)] for both cisplatin and transplatin. Applying nESI-ion trap (IT)-MS showed the advantage of higher sensitivity than the ToF instruments, allowing the detection of bisadducts of oxaliplatin after one week of incubation. In contrast to the ESI mass spectra, MALDI showed a higher degree of fragmentation of the Ub-platinum conjugates. © The Royal Society of Chemistry 2007.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Eidgenössische Technische Hochschule Zürich, University of Florence, École polytechnique fédérale de Lausanne
- Journal
- Journal of Analytical Atomic Spectrometry
- Volume
- 22
- Pages
- 960-967
- No. of pages
- 8
- ISSN
- 0267-9477
- Publication date
- 2007
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/b9a9fa5a-6b0c-49ae-abd4-6832c1dc0ba3