AI Article Synopsis
- Native mass spectrometry (MS) is a crucial technique for studying noncovalent interactions between proteins and ligands, but not all MS methods maintain proteins' natural shapes.
- The demand for quick analysis methods is particularly important in the early phases of drug discovery since most approved and developing drugs interact with targets through these noncovalent interactions.
- This study outlines a rapid approach using IR-MALDESI-MS, achieving approximately 13-second analysis times for noncovalent protein-ligand complexes, specifically testing known binders with carbonic anhydrase and Bruton's tyrosine kinase.
Article Abstract
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.
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| http://dx.doi.org/10.1021/jasms.4c00199 | DOI Listing |
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