Chemical biology approaches for protein tagging in mammalian cells

Understanding the highly dynamic nature of many cellular processes requires techniques that provide access to proteins with precise spatial or temporal control. While genetically encodable tags provide experimental access to a protein of interest, these traditional tags lack adequate spatial or temporal resolution and often add significant bulk to a protein of interest. To this end, chemical biology tagging strategies that can covalently tag proteins with small molecules or noncanonical amino acids can incorporate novel functionalities that allow for increased spatial or temporal control. This review summarizes the current strategies for covalent chemical biology tagging in mammalian cells, emphasizing the advantages, limitations, and recent innovations that can potentially expand the cell biologist's repertoire of tools.