Critical assessment of different methods for quantitative measurement of metallodrug-protein associations
| Autor: | Sarah Theiner, Gunda Koellensperger, Christian R. Kowol, Márkó Grabarics, Stephan Hann, Luis Galvez, Bernhard K. Keppler |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Metal-based anticancer drugs
Organoplatinum Compounds Size-exclusion chromatography Ultrafiltration High-throughput Antineoplastic Agents 010402 general chemistry Mass spectrometry 01 natural sciences Biochemistry Mass Spectrometry Analytical Chemistry Protein purification Metal–protein interaction Humans Inductively coupled plasma mass spectrometry Chromatography High Pressure Liquid Flow injection analysis Chromatography Chemistry 010401 analytical chemistry Blood Proteins Small molecule 0104 chemical sciences Metals Elemental speciation analysis Flow Injection Analysis Chromatography Gel Critical assessment ICP–MS Research Paper Protein Binding |
| Zdroj: | Analytical and Bioanalytical Chemistry |
| ISSN: | 1618-2650 1618-2642 |
| Popis: | 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 abstractQuantitative screening for potential drug–protein binding is an essential step in developingnovel metal-based anticancer drugs Electronic supplementary material The online version of this article (10.1007/s00216-018-1328-8) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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