Insights into the proteome reactivity of electrophiles are crucial for designing activity-based
probes for enzymes lacking cognate affinity labels. Here, we show that different classes of …

Highlights•Electrophiles can show distinct amino-acid selectivities in proteomes.•The
judicious selection of an electrophile is critical to various chemical-proteomic applications.•A …

Protein-reactive electrophiles are critical to chemical proteomic applications including
activity-based protein profiling, site-selective protein modification, and covalent inhibitor …

Targeted covalent inhibitors are powerful entities in drug discovery, but their application has
so far mainly been limited to addressing cysteine residues. The development of cysteine …

Current methods used for measuring amino acid side-chain reactivity lack the throughput
needed to screen large chemical libraries for interactions across the proteome. Here we …

Covalent chemistry is a versatile approach for expanding the ligandability of the human
proteome. Activity-based protein profiling (ABPP) can infer the specific residues modified by …

Activity-based protein profiling (ABPP) serves as a chemical proteomic platform to discover
and characterize functional amino acids in proteins on the basis of their enhanced reactivity …

Nucleophilic amino acids make important contributions to protein function, including
performing key roles in catalysis and serving as sites for post-translational modification …

Despite advances in genetic and proteomic techniques, a complete portrait of the proteome
and its complement of dynamic interactions and modifications remains a lofty, and as of yet …

Proteome profiling by activated esters identified> 9000 ligandable lysines but they are
limited as covalent inhibitors due to poor hydrolytic stability. Here we report our efforts to …