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

• Published in: Chemical science (Cambridge) Vol. 11; no. 26; pp. 6824 - 6829
• Main Authors: Esteoulle, Lucie, Daubeuf, François, Collot, Mayeul, Riché, Stéphanie, Durroux, Thierry, Brasse, David, Marchand, Patrice, Karpenko, Julie, Klymchenko, Andrey S, Bonnet, Dominique
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 14.07.2020; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Aqueous solutions; Chemistry; Chemistry, Multidisciplinary; Dimers; Fluorescent indicators; Imaging; Life Sciences; Near infrared radiation; Physical Sciences; Receptors; Science & Technology; Synthesis; Target recognition; PROTEIN-COUPLED RECEPTORS; FLUORESCENT-PROBES; FAR-RED; LIGAND
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d0sc01018a

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. A near-infrared emitting fluorogenic dimer with environment-sensitive folding and exceptional brightness enables background-free and target-specific imaging of the naturally expressed oxytocin GPCR in living mice.