Review Article | Published:

Chemistry in living systems

Abstract

Dissecting complex cellular processes requires the ability to track biomolecules as they function within their native habitat. Although genetically encoded tags such as GFP are widely used to monitor discrete proteins, they can cause significant perturbations to a protein's structure and have no direct extension to other classes of biomolecules such as glycans, lipids, nucleic acids and secondary metabolites. In recent years, an alternative tool for tagging biomolecules has emerged from the chemical biology community—the bioorthogonal chemical reporter. In a prototypical experiment, a unique chemical motif, often as small as a single functional group, is incorporated into the target biomolecule using the cell's own biosynthetic machinery. The chemical reporter is then covalently modified in a highly selective fashion with an exogenously delivered probe. This review highlights the development of bioorthogonal chemical reporters and reactions and their application in living systems.

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Acknowledgements

J.A.P. is supported by a Howard Hughes Medical Institute predoctoral fellowship. We thank N. Agard, J. Baskin, I. Carrico, D. Dube, S. Laughlin and C. McVaugh for critical reading of the manuscript.

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The authors declare no competing financial interests.

Correspondence to Carolyn R Bertozzi.

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Figure 1: Composition of a typical mammalian cell11.
Figure 2: The bioorthogonal chemical reporter strategy.
Figure 3: Bioorthogonal chemical reporters and cellular imaging.
Figure 4: The Staudinger ligation.
Figure 5: Methods for introducing chemical reporters into proteins.
Figure 6: Azides can be incorporated into glycoconjugates using glycan biosynthetic pathways.