Protein organic chemistry and applications for labeling and engineering in live-cell systems

Angew Chem Int Ed Engl. 2013 Apr 8;52(15):4088-106. doi: 10.1002/anie.201207089. Epub 2013 Feb 20.


The modification of proteins with synthetic probes is a powerful means of elucidating and engineering the functions of proteins both in vitro and in live cells or in vivo. 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 tag-probe 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 2-4 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.

Publication types

  • Review

MeSH terms

  • Amino Acids / chemistry
  • Animals
  • Cell Survival
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Engineering*
  • Proteins / chemistry*
  • Staining and Labeling*


  • Amino Acids
  • Proteins