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  4. Mass spectrometric analysis of ubiquitin-platinum interactions of leading anticancer drugs: MALDI versus ESI
 
research article

Mass spectrometric analysis of ubiquitin-platinum interactions of leading anticancer drugs: MALDI versus ESI

Hartinger, Christian G.
•
Ang, Wee Han  
•
Casini, Angela  
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2007
JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY

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 anal. 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 anal. Cisplatin, transplatin and oxaliplatin formed mainly monoadducts with Ub, but of significantly different compn. 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 anal. methods provide comparable results. However, the higher resoln. 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.

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Type
research article
DOI
10.1039/b703350h
Web of Science ID

WOS:000248281200014

Author(s)
Hartinger, Christian G.
Ang, Wee Han  
Casini, Angela  
Messori, Luigi
Keppler, Bernhard K.
Dyson, Paul J.  
Date Issued

2007

Published in
JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY
Volume

22

Issue

8

Start page

960

End page

967

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCOM  
Available on Infoscience
December 13, 2007
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/15627
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