Versatile Tool for the Analysis of Metal–Protein Interactions Reveals the Promiscuity of Metallodrug–Protein Interactions
| Autor: | Ronald F. S. Lee, Daniel Ortiz, Paul J. Dyson, Laure Menin, Luc Patiny |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Electrospray
Erythrocytes Meat Stereochemistry Aquation 010402 general chemistry 01 natural sciences Analytical Chemistry Protein–protein interaction Adduct chemistry.chemical_compound Ubiquitin medicine Animals Horses Binding site Muscle Skeletal Cisplatin biology Myoglobin Chemistry 010401 analytical chemistry 0104 chemical sciences Pharmaceutical Preparations Biophysics biology.protein Cattle DNA medicine.drug |
| Zdroj: | Analytical Chemistry. 89:11985-11989 |
| ISSN: | 1520-6882 0003-2700 |
| DOI: | 10.1021/acs.analchem.7b02211 |
| Popis: | Metallodrug-protein interactions contribute to their therapeutic effect (even when DNA is the dominant target), side-effects and are implicit in drug resistance. Here, we provide mass spectrometric-based evidence to show that metallodrug interactions with proteins are considerably more complex than current literature would suggest. Using native-like incubation and electrospray conditions together with an automated tool we designed for exhaustive mass spectra matching, the promiscuity of binding of cisplatin to ubiquitin is revealed, with 14 different binding sites observed. There is a binding preference to negatively charged sites on the protein, consistent with the cationic nature of the cisplatin adduct following aquation. These results have implications in metallodrug development and beyond to the toxicological effects of metal ions more generally. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|