Protein Organic Chemistry and Applications for Labeling and Engineering in Live-Cell Systems

The modification of proteins with synthetic probes is a powerful means of elucidating and engineering the functions of proteins both invitro and in live cells or invivo. Herein we review recent progress in chemistry-based protein modification methods and their application in protein engineering, with particular emphasis on the following four strategies: 1)the bioconjugation reactions of amino acids on the surfaces of natural proteins, mainly applied in test-tube settings; 2)the bioorthogonal reactions of proteins with non-natural functional groups; 3)the coupling of recognition and reactive sites using an enzyme or short peptide tagprobe pair for labeling natural amino acids; and 4)ligand-directed labeling chemistries for the selective labeling of endogenous proteins in living systems. Overall, these techniques represent a useful set of tools for application in chemical biology, with the methods 24 in particular being applicable to crude (living) habitats. Although still in its infancy, the use of organic chemistry for the manipulation of endogenous proteins, with subsequent applications in living systems, represents a worthy challenge for many chemists.