Back
Luciferase-induced photoreductive uncaging of small-molecule effectors.
Journal article

Luciferase-induced photoreductive uncaging of small-molecule effectors.

  • Lindberg E Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, 30 quai Ernest Ansermet, 1211, Geneva, Switzerland.
  • Angerani S Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, 30 quai Ernest Ansermet, 1211, Geneva, Switzerland.
  • Anzola M Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, 30 quai Ernest Ansermet, 1211, Geneva, Switzerland.
  • Winssinger N Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, 30 quai Ernest Ansermet, 1211, Geneva, Switzerland. Nicolas.Winssinger@unige.ch.
  • 2018-09-01
Published in:
  • Nature communications. - 2018
Bioluminescence Resonance Energy Transfer Techniques
Luciferases
Luminescent Proteins
Photochemistry
Pyrazoles
Pyrimidines
Rhodamines
English Bioluminescence resonance energy transfer (BRET) is extensively used to study dynamic systems and has been utilized in sensors for studying protein proximity, metabolites, and drug concentrations. Herein, we demonstrate that BRET can activate a ruthenium-based photocatalyst which performs bioorthogonal reactions. BRET from luciferase to the ruthenium photocatalyst is used to uncage effector molecules with up to 64 turnovers of the catalyst, achieving concentrations >0.6 μM effector with 10 nM luciferase construct. Using a BRET sensor, we further demonstrate that the catalysis can be modulated in response to an analyte, analogous to allosterically controlled enzymes. The BRET-induced reaction is used to uncage small-molecule drugs (ibrutinib and duocarmycin) at biologically effective concentrations in cellulo.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/232786
Statistics
Document views: 22 File downloads: