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research article

Reactivity of anticancer metallodrugs with serum proteins: New insights from size exclusion chromatography-ICP-MS and ESI-MS

Groessl, Michael  
•
Terenghi, Mattia
•
Casini, Angela  
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2010
Journal of Analytical Atomic Spectrometry

A method based on the coupling of high resolution size-exclusion liquid chromatography using a polymer stationary phase with inductively coupled plasma mass spectrometry was developed to study the interactions of two metallodrugs - cisplatin and RAPTA-T - with the serum proteins albumin and transferrin. In contrast to previous approaches, the technique allowed the total recovery of the metals from the column and was able to discriminate between the different species of the metallodrugs and their complexes with the proteins at femtomolar detection levels. Metal binding was found to be dependent on the protein concentration and on the incubation time of the sample. Cisplatin was found to bind the serum proteins to the same extent, whereas RAPTA-T showed marked preference for transferrin. The affinity of the ruthenium complex for holo-transferrin was higher than for the apoform suggesting a cooperative iron-mediated metal binding mechanism. RAPTA-T binding to holotransferrin was further investigated by electrospray mass spectrometry using both the intact protein and a model peptide mimicking the iron-binding pocket.

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Type
research article
DOI
10.1039/b922701f
Web of Science ID

WOS:000274961600006

Author(s)
Groessl, Michael  
Terenghi, Mattia
Casini, Angela  
Elviri, Lisa
Lobinski, Ryszard
Dyson, Paul J.  
Date Issued

2010

Publisher

Royal Society of Chemistry

Published in
Journal of Analytical Atomic Spectrometry
Volume

25

Issue

3

Start page

305

End page

313

Subjects

Plasma-Mass Spectrometry

•

Organometallic Ruthenium Compound

•

Multidimensional Liquid-Chromatography

•

Platinum Antitumor Chemistry

•

Capillary-Electrophoresis

•

Escherichia-Coli

•

Binding-Sites

•

Cisplatin Binding

•

Complexes

•

Transferrin

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCOM  
Available on Infoscience
December 15, 2010
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/62157
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