title: Mapping proteome-wide interactions of reactive chemicals using chemoproteomic platforms.
abstract: A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these irreversible agents directly in complex biological systems. We review here several chemoproteomic strategies that have facilitated our understanding of specific protein interactions of irreversibly-acting pharmaceuticals, endogenous metabolites, and environmental electrophiles to reveal novel pharmacological, biological, and toxicological mechanisms.
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Counihan
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: Breanna
authors.initials: B
authors.lastname: Ford
authors.affiliation: Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, United States. Electronic address: dnomura@berkeley.edu.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Nomura
mesh_terms: D000818:Animals; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D054852:Small Molecule Libraries / Q000378:metabolism; D014116:Toxicology
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins; D054852:Small Molecule Libraries