Activity-Based Hydrazine Probes for Protein Profiling of Electrophilic Functionality in Therapeutic Targets.

ABSTRACT: Most known probes for activity-based protein profiling (ABPP) use electrophilic groups that tag a single type of nucleophilic amino acid to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electrophilic enzyme cofactors, transient intermediates, and labile regulatory modifications, but ABPP probes for such species are underdeveloped. Here, we describe a versatile class of probes for this less charted hemisphere of the proteome. The use of an electron-rich hydrazine as the common chemical modifier enables covalent targeting of multiple, pharmacologically important classes of enzymes bearing diverse organic and inorganic cofactors. Probe attachment occurs by both polar and radicaloid mechanisms, can be blocked by molecules that occupy

SUBMITTER: Lin Z 

PROVIDER: S-EPMC8461768 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature