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  • Title: Luciferase-Induced Photouncaging: Bioluminolysis.
    Author: Chang D, Lindberg E, Feng S, Angerani S, Riezman H, Winssinger N.
    Journal: Angew Chem Int Ed Engl; 2019 Nov 04; 58(45):16033-16037. PubMed ID: 31478317.
    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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