Detection of Noncovalent Protein-Ligand Complexes by IR-MALDESI-MS.
| Autor: | Knizner KT; FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States., Pu F; Discovery Research, AbbVie Inc., North Chicago, Illinois 60064, United States., Sawicki JW; Discovery Research, AbbVie Inc., North Chicago, Illinois 60064, United States., Radosevich AJ; Discovery Research, AbbVie Inc., North Chicago, Illinois 60064, United States., Ugrin SA; Discovery Research, AbbVie Inc., North Chicago, Illinois 60064, United States., Elsen NL; Discovery Research, AbbVie Inc., North Chicago, Illinois 60064, United States., Williams JD; Discovery Research, AbbVie Inc., North Chicago, Illinois 60064, United States., Muddiman DC; FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of the American Society for Mass Spectrometry [J Am Soc Mass Spectrom] 2024 Aug 07; Vol. 35 (8), pp. 1913-1920. Date of Electronic Publication: 2024 Jul 11. |
| DOI: | 10.1021/jasms.4c00199 |
| Abstrakt: | Native mass spectrometry (MS) is a powerful analytical technique to directly probe noncovalent protein-protein and protein-ligand interactions. However, not every MS platform can preserve proteins in their native conformation due to high energy deposition from the utilized ionization source. Most small molecules approved as drugs and in development interact with their targets through noncovalent interactions. Therefore, rapid methods to analyze noncovalent protein-ligand interactions are necessary for the early stages of the drug discovery pipeline. Herein, we describe a method for analyzing noncovalent protein-ligand complexes by IR-MALDESI-MS with analysis times of ∼13 s per sample. Carbonic anhydrase and the kinase domain of Bruton's tyrosine kinase are paired with known noncovalent binders to evaluate the effectiveness of native MS by IR-MALDESI. |
| Databáze: | MEDLINE |
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