Luciferase-induced photoreductive uncaging of small-molecule effectors

Nature Communications
Eric LindbergNicolas Winssinger

Abstract

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.

References

Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Anca Dragulescu-AndrasiSanjiv S Gambhir
Dec 31, 2011·Organic Letters·Manuel RöthlingshöferNicolas Winssinger
Nov 29, 2012·Journal of the American Chemical Society·Kalyan K SadhuNicolas Winssinger
May 2, 2013·Chemistry : a European Journal·Kalyan K Sadhu, Nicolas Winssinger
Jun 14, 2013·Cancer Biology & Therapy·George A VielhauerDale Boger
Jun 9, 2014·Nature Chemical Biology·Rudolf GrissKai Johnsson
May 27, 2015·ACS Chemical Biology·Thomas MachleidtKeith V Wood
Jul 23, 2015·Nature Communications·Alberto SchenaKai Johnsson
Jan 7, 2016·Proceedings of the National Academy of Sciences of the United States of America·Ken BerglundUte Hochgeschwender
Jun 16, 2016·Scientific Reports·Elise GoyetJulie Perroy
Jul 15, 2016·ACS Central Science·Laurent HoltzerNicolas Winssinger
Oct 22, 2016·ACS Chemical Biology·Stijn J A AperMaarten Merkx
Jan 19, 2017·Journal of the American Chemical Society·Dalu ChangNicolas Winssinger
May 5, 2017·ACS Central Science·Roger R NaniMartin J Schnermann
Sep 2, 2017·Journal of Neuroscience Research·Sung Young ParkUte Hochgeschwender
Sep 5, 2017·Nature Methods·Hsien-Wei YehHui-Wang Ai

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Citations

Jan 29, 2019·Chemistry : a European Journal·Simona Angerani, Nicolas Winssinger
Sep 4, 2019·Angewandte Chemie·Dalu ChangNicolas Winssinger
Feb 21, 2019·Annual Review of Analytical Chemistry·Hsien-Wei Yeh, Hui-Wang Ai
Nov 27, 2020·Biochemical Society Transactions·Lieuwe BiewengaMaarten Merkx
Sep 30, 2020·Chemistry : a European Journal·Paolo DestitoJosé L Mascareñas
Feb 11, 2021·Journal of the American Chemical Society·Emma E WatsonNicolas Winssinger
Dec 14, 2019·ACS Synthetic Biology·Kshitij Parag-SharmaAntonio L Amelio
Mar 9, 2021·Journal of the American Chemical Society·Dalu ChangNicolas Winssinger
Mar 19, 2021·Chemical Society Reviews·Aisha J Syed, James C Anderson
Aug 17, 2020·Cell Chemical Biology·Anna C Love, Jennifer A Prescher
Mar 27, 2021·Current Opinion in Chemical Biology·Giorgia ZambitoLaura Mezzanotte
Jun 8, 2021·Chemical Science·Alex ManicardiAnnemieke Madder
Jun 17, 2020·Journal of the American Chemical Society·Simona Angerani, Nicolas Winssinger
Sep 21, 2019·Journal of the American Chemical Society·Ki Tae KimNicolas Winssinger
Dec 14, 2021·Journal of the American Chemical Society·Edward B PimentelJeffrey D Martell

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Methods Mentioned

BETA
BRET
FCS

Software Mentioned

Leica
LUCID
LUPIN
MetaXpress®

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