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Luciferase-Induced Photouncaging: Bioluminolysis

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Published in Angewandte Chemie. 2019, vol. 58, no. 45, p. 16033-16037
Abstract Bioluminescence resonance energy transfer (BRET) has been widely used for studying dynamic processes in biological systems such as protein–protein interactions and other signaling events. Aside from acting as a reporter, BRET can also turn on functions in living systems. Herein, we report the application of BRET to performing a biorthogonal reaction in living cells; namely, releasing functional molecules through energy transfer to a coumarin molecule, a process termed bioluminolysis. An efficient BRET from Nanoluc‐Halotag chimera protein (H‐Luc) to a coumarin substrate yields the excited state of coumarin, which in turn triggers hydrolysis to uncage a target molecule. Compared to the conventional methods, this novel uncaging system requires no external light source and shows fast kinetics (t1/2<2 min). We applied this BRET uncaging system to release a potent kinase inhibitor, ibrutinib, in living cells, highlighting its broad utility in controlling the supply of bioactive small molecules in vivo.
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Other version: http://doi.wiley.com/10.1002/anie.201907734
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Research groups Groupe Riezman
Groupe Winssinger
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CHANG, Dalu et al. Luciferase-Induced Photouncaging: Bioluminolysis. In: Angewandte Chemie: International Edition, 2019, vol. 58, n° 45, p. 16033-16037. doi: 10.1002/anie.201907734 https://archive-ouverte.unige.ch/unige:125191

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Deposited on : 2019-10-29

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