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Development and application of bond cleavage reactions in bioorthogonal chemistry

Nature Chemical Biology volume 12, pages 129–137 (2016)Cite this article

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Abstract

Bioorthogonal chemical reactions are a thriving area of chemical research in recent years as an unprecedented technique to dissect native biological processes through chemistry-enabled strategies. However, current concepts of bioorthogonal chemistry have largely centered on 'bond formation' reactions between two mutually reactive bioorthogonal handles. Recently, in a reverse strategy, a collection of 'bond cleavage' reactions has emerged with excellent biocompatibility. These reactions have expanded our bioorthogonal chemistry repertoire, enabling an array of exciting new biological applications that range from the chemically controlled spatial and temporal activation of intracellular proteins and small-molecule drugs to the direct manipulation of intact cells under physiological conditions. Here we highlight the development and applications of these bioorthogonal cleavage reactions. Furthermore, we lay out challenges and propose future directions along this appealing avenue of research.

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Figure 1: Representatives of bioorthogonal ligation reactions.
Figure 2: Emerging bioorthogonal cleavage reactions.
Figure 3: Bioorthogonal cleavage chemistry for protein activation.
Figure 4: Bioorthogonal cleavage chemistry for cell engineering.
Figure 5: Bioorthogonal cleavage chemistry on small molecules.
Figure 6: Outlook for bioorthogonal cleavage chemistry.

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Acknowledgements

Our research interests in expanding the bioorthogonal chemistry toolkit have been generously supported by the National Natural Science Foundation of China (21225206, 21521003 and 21432002) and the National Basic Research Program of China (2012CB917301).

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  1. Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China

    Jie Li & Peng R Chen

  2. Peking-Tsinghua Center for Life Sciences, Beijing, China

    Peng R Chen

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P.R.C. and J.L. wrote the manuscript and prepared the figures.

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Correspondence to Peng R Chen.

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Li, J., Chen, P. Development and application of bond cleavage reactions in bioorthogonal chemistry. Nat Chem Biol 12, 129–137 (2016). https://doi.org/10.1038/nchembio.2024

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