Abstract
Small molecules that specifically activate an intracellular protein of interest are highly desirable. A generally applicable strategy, however, remains elusive. Herein we describe a small molecule–triggered bioorthogonal protein decaging technique that relies on the inverse electron-demand Diels-Alder reaction for eliminating a chemically caged protein side chain within living cells. This method permits the efficient activation of a given protein (for example, an enzyme) in its native cellular context within minutes.
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Acknowledgements
We acknowledge support from R. Meng and the Proteomic Mass Spectrometry Core of the National Facilities for Protein Sciences (the Phoenix Project) at Peking University. This work was supported by the National Basic Research Program of China (2010CB912300 and 2012CB917301) and the National Natural Science Foundation of China (21225206 and 91313301). J.L. acknowledges support from the Peking University Principal Foundation. S.F. Reichard edited the manuscript.
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P.R.C. and J.L. designed the experimental strategy and wrote the manuscript. J.L. and S.J. performed the experiments. All authors prepared the figures and edited the manuscript.
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Supplementary Note, Supplementary Results, Supplementary Table 1 and Supplementary Figures 1–21. (PDF 4649 kb)
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Li, J., Jia, S. & Chen, P. Diels-Alder reaction–triggered bioorthogonal protein decaging in living cells. Nat Chem Biol 10, 1003–1005 (2014). https://doi.org/10.1038/nchembio.1656
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DOI: https://doi.org/10.1038/nchembio.1656
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