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Luciferase‐Induced Photouncaging: Bioluminolysis
Author(s) -
Chang Dalu,
Lindberg Eric,
Feng Suihan,
Angerani Simona,
Riezman Howard,
Winssinger Nicolas
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201907734
Subject(s) - bioluminescence , chemistry , luciferase , förster resonance energy transfer , biophysics , coumarin , small molecule , molecule , in vivo , energy transfer , fluorescence , biochemistry , microbiology and biotechnology , biology , transfection , physics , organic chemistry , quantum mechanics , molecular physics , gene
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 ( t 1/2 <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.