Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs.

ABSTRACT: Comparative, dose-dependent analysis of interactions between small molecule drugs and their targets, as well as off-target interactions, in complex proteomes is crucial for selecting optimal drug candidates. The affinity of small molecules for targeted proteins is largely dictated by interactions between amino acid side chains and these drugs. Thus, studying drug-protein interactions at an amino acid resolution provides a comprehensive understanding of the drug selectivity and efficacy. In this study, we further refined the site-specific activity-based protein profiling strategy (ABPP), PhosID-ABPP, on a timsTOF HT mass spectrometer. This refinement enables dual dose-dependent competition of inhibitors within a single cellular proteome. Here, a comparative analysis of two activity-based pr

SUBMITTER: van Bergen W 

PROVIDER: S-EPMC11334109 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature