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A near-infrared fluorogenic dimer enables background-free imaging of endogenous GPCRs in living mice†
Lucie Esteoulle,François Daubeuf,Mayeul Collot,Stéphanie Riché,Thierry Durroux,David Brasse,Patrice Marchand,Julie Karpenko,Andrey S. Klymchenko,Dominique Bonnet
Chemical Science Pub Date : 06/17/2020 00:00:00 , DOI:10.1039/D0SC01018A
Abstract

Fluorescent probes are commonly used in studying G protein-coupled receptors in living cells; however their application to the whole animal receptor imaging is still challenging. To address this problem, we report the design and the synthesis of the first near-infrared emitting fluorogenic dimer with environment-sensitive folding. Due to the formation of non-fluorescent H-aggregates in an aqueous medium, the near-infrared fluorogenic dimer displays a strong turn-on response (up to 140-fold) in an apolar environment and exceptional brightness: 56% quantum yield and ≈444 000 M−1 cm−1 extinction coefficient. Grafted on a ligand of the oxytocin receptor, it allows the unprecedented background-free and target-specific imaging of the naturally expressed receptor in living mice.

Graphical abstract: A near-infrared fluorogenic dimer enables background-free imaging of endogenous GPCRs in living mice
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