Site-Specific Competitive Kinase Inhibitor Target Profiling Using Phosphonate Affinity Tags.

ABSTRACT: Protein kinases are prime targets for drug development due to their involvement in various cancers. However, selective inhibition of kinases, while avoiding off-target effects remains a significant challenge for the development of protein kinase inhibitors. Activity-based protein profiling (ABPP), in combination with pan-kinase activity-based probes (ABPs) and mass spectrometry-based proteomics, enables the identification of kinase drug targets. Here, we extend existing ABPP strategies for kinase profiling with a site-specific analysis, allowing for protein kinase inhibitor target engagement profiling with amino acid specificity. The site-specific approach involves highly efficient enrichment of ABP-labeled peptides, resulting in a less complex peptide matrix, straightforward data analysis

SUBMITTER: van Bergen W 

PROVIDER: S-EPMC11889359 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature