Critical assessment of different methods for quantitative measurement of metallodrug-protein associations

Analytical and Bioanalytical Chemistry
Luis GalvezGunda Koellensperger

Abstract

Quantitative screening for potential drug-protein binding is an essential step in developing novel metal-based anticancer drugs. ICP-MS approaches are at the core of this task; however, many applications lack in the capability of large-scale high-throughput screenings and proper validation. In this work, we critically discuss the analytical figures of merit and the potential method-based quantitative differences applying four different ICP-MS strategies to ex vivo drug-serum incubations. Two candidate drugs, more specifically, two Pt(IV) complexes with known differences of binding affinity towards serum proteins were selected. The study integrated centrifugal ultrafiltration followed by flow injection analysis, turbulent flow chromatography (TFC), and size exclusion chromatography (SEC), all combined with inductively coupled plasma-mass spectrometry (ICP-MS). As a novelty, for the first time, UHPLC SEC-ICP-MS was implemented to enable rapid protein separation to be performed within a few minutes at > 90% column recovery for protein adducts and small molecules. Graphical abstract Quantitative screening for potential drug-protein binding is an essential step in developingnovel metal-based anticancer drugs.

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Citations

Apr 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katarina MarkovićJanez Ščančar
Mar 27, 2020·Neural Regeneration Research·Andrijana LazicMilena Stevanović
Jul 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mathilde BouchéStéphane Bellemin-Laponnaz
Dec 8, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Ammar M EbrahimBernhard Michalke
Oct 8, 2020·Biomedical Chromatography : BMC·Edouard C Nice
Feb 4, 2021·Current Opinion in Chemical Biology·Sarah TheinerGunda Koellensperger

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Methods Mentioned

BETA
electrophoresis
FCS

Software Mentioned

Work
Qtegra Intelligent Scientific Data Solution
Agilent MassHunter
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