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Article Dans Une Revue ACS Chemical Biology Année : 2021

Nile Red-Based GPCR Ligands as Ultrasensitive Probes of the Local Lipid Microenvironment of the Receptor

Christel Valencia
  • Fonction : Auteur
Pascal Villa
Andrey S Klymchenko
Julie Karpenko
Iuliia A Karpenko
  • Fonction : Auteur

Résumé

The local lipid microenvironment of transmembrane receptors is an essential factor in Gprotein coupled receptor (GPCR) signaling. However, tools are currently missing for studying endogenously expressed GPCRs in primary cells and tissues. Here we introduce fluorescent environment-sensitive GPCR ligands for probing the microenvironment of the receptor in living cells using fluorescence microscopy under no-wash conditions. We designed and synthesized antagonist ligands of the oxytocin receptor (OTR) by conjugating a high-affinity non-peptidic OTR ligand PF-3274167 to the environment-sensitive fluorescent dye Nile Red. The length of the polar PEG spacer between the pharmacophore and the fluorophore was adjusted to lower the non-specific interactions of the probe while preserving a strong fluorogenic response. We demonstrated that the new probes embed into the lipid bilayer in the vicinity of the receptor and convey the information about the local polarity and the lipid order via the wavelength-shifting emission of the Nile Red fluorophore.
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Dates et versions

hal-03437257 , version 1 (19-11-2021)

Identifiants

Citer

Fabien Hanser, Claire Marsol, Christel Valencia, Pascal Villa, Andrey S Klymchenko, et al.. Nile Red-Based GPCR Ligands as Ultrasensitive Probes of the Local Lipid Microenvironment of the Receptor. ACS Chemical Biology, 2021, 16 (4), pp.651-660. ⟨10.1021/acschembio.0c00897⟩. ⟨hal-03437257⟩
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