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Luciferase‐Induced Photouncaging: Bioluminolysis

Authors: Dalu Chang; Eric Lindberg; Suihan Feng; Simona Angerani; Howard Riezman; Nicolas Winssinger;

Luciferase‐Induced Photouncaging: Bioluminolysis

Abstract

AbstractBioluminescence 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.

Country
Switzerland
Related Organizations
Subjects by Vocabulary

Microsoft Academic Graph classification: Kinetics Turn (biochemistry) chemistry.chemical_compound In vivo Bioluminescence Luciferase Kinase Coumarin Small molecule chemistry Biophysics

Dewey Decimal Classification: ddc:540

Keywords

Catalysis, Piperidines, Coumarins, Fluorescence Resonance Energy Transfer, Humans, Luciferases, Adenine, General Chemistry, Luminescent Proteins, Pyrimidines, Luminescent Measurements, Pyrazoles, HeLa Cells, Protein Binding

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    impulse
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    Top 10%
  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    17
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
17
Top 10%
Average
Top 10%
Funded by
SNSF| Probes for chemical biology: from synthesis to biosupramolecular systems
Project
  • Funder: Swiss National Science Foundation (SNSF)
  • Project Code: 169141
  • Funding stream: Projects | Project funding
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