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

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 …

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

Chemical modification of proteins provides powerful tools to realize a broad range of
exciting biological applications, including the development of new classes of …

The use of synthetic molecules to modulate and track biological events is a central
component of chemical biology. As a result, the precise, covalent modification of …

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

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 …

Targeting noncatalytic cysteine residues with irreversible acrylamide-based inhibitors is a
powerful approach for enhancing pharmacological potency and selectivity. Nevertheless …

Covalent modification can expand a protein's functional capacity. Fluorescent or radioactive
labeling, for instance, allows imaging of a protein in real time. Labeling with an affinity probe …

In the past decade, numerous chemical technologies have been developed to allow the site-
specific post-translational modification of proteins. Traditionally covalent chemical protein …