ACS Publications. Most Trusted. Most Cited. Most Read
Nile Red-Based GPCR Ligands as Ultrasensitive Probes of the Local Lipid Microenvironment of the Receptor
My Activity
    Articles

    Nile Red-Based GPCR Ligands as Ultrasensitive Probes of the Local Lipid Microenvironment of the Receptor
    Click to copy article linkArticle link copied!

    • Fabien Hanser
      Fabien Hanser
      Laboratoire d’Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Strasbourg Drug Discovery and Development Institute (IMS), 74 route du Rhin, 67401 Illkirch-Graffenstaden, France
    • Claire Marsol
      Claire Marsol
      Laboratoire d’Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Strasbourg Drug Discovery and Development Institute (IMS), 74 route du Rhin, 67401 Illkirch-Graffenstaden, France
      Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), UMS 3286 CNRS/Université de Strasbourg, Strasbourg Drug Discovery and Development Institute (IMS), ESBS Pôle API, Bld Sébastien Brant, 67412 Illkirch-Graffenstaden, France
    • Christel Valencia
      Christel Valencia
      Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), UMS 3286 CNRS/Université de Strasbourg, Strasbourg Drug Discovery and Development Institute (IMS), ESBS Pôle API, Bld Sébastien Brant, 67412 Illkirch-Graffenstaden, France
    • Pascal Villa
      Pascal Villa
      Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), UMS 3286 CNRS/Université de Strasbourg, Strasbourg Drug Discovery and Development Institute (IMS), ESBS Pôle API, Bld Sébastien Brant, 67412 Illkirch-Graffenstaden, France
      More by Pascal Villa
    • Andrey S. Klymchenko
      Andrey S. Klymchenko
      Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS/Université de Strasbourg, 74 route du Rhin, 67401 Illkirch-Graffenstaden, France
    • Dominique Bonnet*
      Dominique Bonnet
      Laboratoire d’Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Strasbourg Drug Discovery and Development Institute (IMS), 74 route du Rhin, 67401 Illkirch-Graffenstaden, France
      *E-mail: [email protected]
    • Julie Karpenko*
      Julie Karpenko
      Laboratoire d’Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Strasbourg Drug Discovery and Development Institute (IMS), 74 route du Rhin, 67401 Illkirch-Graffenstaden, France
      *E-mail: [email protected]
    Other Access OptionsSupporting Information (1)

    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2021, 16, 4, 651–660
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschembio.0c00897
    Published March 18, 2021
    Copyright © 2021 American Chemical Society

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    The local lipid microenvironment of transmembrane receptors is an essential factor in G protein 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 nonpeptidic 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 nonspecific 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 information about the local polarity and the lipid order via the wavelength-shifting emission of the Nile Red fluorophore.

    Copyright © 2021 American Chemical Society

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acschembio.0c00897.

    • Synthetic procedures, absorption and steady-state fluorescence measurements, functional characterization of the OTR ligands, cytotoxicity study (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai

    This article is cited by 20 publications.

    1. Lucille Weiss, Dominique Bonnet, Dmytro Dziuba, Julie Karpenko. Flow Cytometry Analysis of Perturbations in the Bacterial Cell Envelope Enabled by Monitoring Generalized Polarization of the Solvatochromic Peptide UNR-1. Analytical Chemistry 2025, 97 (1) , 622-628. https://doi.org/10.1021/acs.analchem.4c04953
    2. Lucille Weiss, Antoine Mirloup, Léa Blondé, Hanna Manko, Jean Peluso, Dominique Bonnet, Dmytro Dziuba, Julie Karpenko. Fluorescent Antimicrobial Peptides Based on Nile Red: Effect of Conjugation Site and Chemistry on Wash-Free Staining of Bacteria. Bioconjugate Chemistry 2024, 35 (11) , 1779-1787. https://doi.org/10.1021/acs.bioconjchem.4c00331
    3. Yani Liu, Xiangjie Luo, Wei Cheng, Ling Zhou, Yang Zhou, Hai-Liang Zhu, Tony D. James, Yong Qian. Mapping of β3-Adrenergic Receptor in Living Cells with a Ligand-Guided Fluorescent Probe. Analytical Chemistry 2024, 96 (45) , 18020-18028. https://doi.org/10.1021/acs.analchem.4c03408
    4. Yufeng Xiao, Jing Chen, Shaoxian Li, Qing Zhang, Yin Liu, Linhai Chen, Yadi Sun, Min Gu, Xin Xie, Fajun Nan. Discovery of GPR84 Fluorogenic Probes Based on a Novel Antagonist for GPR84 Bioimaging. Journal of Medicinal Chemistry 2024, 67 (13) , 10875-10890. https://doi.org/10.1021/acs.jmedchem.4c00359
    5. Rémi Pelletier, Dmytro I. Danylchuk, Hela Benaissa, Fanny Broch, Romain Vauchelles, Arnaud Gautier, Andrey S. Klymchenko. Genetic Targeting of Solvatochromic Dyes for Probing Nanoscale Environments of Proteins in Organelles. Analytical Chemistry 2023, 95 (22) , 8512-8521. https://doi.org/10.1021/acs.analchem.3c00515
    6. Wenhua Li, Zhao Ma, Lupei Du, Minyong Li. Development and Characterization of a Highly Selective Turn-On Fluorescent Ligand for β3-Adrenergic Receptor. Analytical Chemistry 2023, 95 (5) , 2848-2856. https://doi.org/10.1021/acs.analchem.2c04269
    7. Andrey S. Klymchenko. Fluorescent Probes for Lipid Membranes: From the Cell Surface to Organelles. Accounts of Chemical Research 2023, 56 (1) , 1-12. https://doi.org/10.1021/acs.accounts.2c00586
    8. Wenhua Li, Zhao Ma, Jiwei Chen, Gaopan Dong, Lupei Du, Minyong Li. Discovery of Environment-Sensitive Fluorescent Ligands of β-Adrenergic Receptors for Cell Imaging and NanoBRET Assay. Analytical Chemistry 2022, 94 (19) , 7021-7028. https://doi.org/10.1021/acs.analchem.1c05646
    9. Renáta Szabó, Ágnes Hornyánszky, Dóra Judit Kiss, György Miklós Keserű. Fluorescent tools for imaging class A G-protein coupled receptors. European Journal of Pharmaceutical Sciences 2025, 209 , 107074. https://doi.org/10.1016/j.ejps.2025.107074
    10. Yuhui Wang, Hengke Guo, Wang Wan, Biao Jing, Yulong Bai, Jialu Sun, Xin Zhang, Zhenming Gao, Yu Liu, Xuepeng Dong. A Solvatochromic and Photosensitized Lipid Droplet Probe Detects Local Polarity Heterogeneity and Labels Interacting Proteins in Human Liver Disease Tissue. Advanced Healthcare Materials 2025, 14 (7) https://doi.org/10.1002/adhm.202404713
    11. Pablo Carravilla, Luca Andronico, Jan Schlegel, Yagmur B. Urem, Ellen Sjule, Franziska Ragaller, Florian Weber, Cenk O. Gurdap, Yavuz Ascioglu, Taras Sych, Joseph Lorent, Erdinc Sezgin. Measuring plasma membrane fluidity using confocal microscopy. Nature Protocols 2025, 9 https://doi.org/10.1038/s41596-024-01122-8
    12. Antoine Mirloup, Yann Berthomé, Stéphanie Riché, Patrick Wagner, Fabien Hanser, Arthur Laurent, Xavier Iturrioz, Catherine Llorens‐Cortes, Julie Karpenko, Dominique Bonnet. Alared: Solvatochromic and Fluorogenic Red Amino Acid for Ratiometric Live‐Cell Imaging of Bioactive Peptides. Chemistry – A European Journal 2024, 30 (35) https://doi.org/10.1002/chem.202401296
    13. Vasyl G. Pivovarenko, Andrey S. Klymchenko. Fluorescent Probes Based on Charge and Proton Transfer for Probing Biomolecular Environment. The Chemical Record 2024, 24 (2) https://doi.org/10.1002/tcr.202300321
    14. Alexander P Demchenko. Dual emission and its λ-ratiometric detection in analytical fluorimetry. Pt. I. Basic mechanisms of generating the reporter signal. Methods and Applications in Fluorescence 2023, 11 (3) , 033002. https://doi.org/10.1088/2050-6120/acc714
    15. Yan Jia, Lili Xu, Lancheng Wang, Kun Yan, Jieru Chen, Pengcheng Xu, Bin Di, Fang Yan, Chi Hu. A light-up fluorescence probe for wash-free analysis of Mu-opioid receptor and ligand-binding events. Analytica Chimica Acta 2023, 1261 , 341220. https://doi.org/10.1016/j.aca.2023.341220
    16. Pragati K. Prasad, Noa Eizenshtadt, Inna Goliand, Liat Fellus-Alyagor, Roni Oren, Ofra Golani, Leila Motiei, David Margulies. Chemically programmable bacterial probes for the recognition of cell surface proteins. Materials Today Bio 2023, 20 , 100669. https://doi.org/10.1016/j.mtbio.2023.100669
    17. Miwa Umebayashi, Satoko Takemoto, Luc Reymond, Mayya Sundukova, Ruud Hovius, Annalisa Bucci, Paul A. Heppenstall, Hideo Yokota, Kai Johnsson, Howard Riezman. A covalently linked probe to monitor local membrane properties surrounding plasma membrane proteins. Journal of Cell Biology 2023, 222 (3) https://doi.org/10.1083/jcb.202206119
    18. Giacomo Renno, Francesca Cardano, Viktoria Ilieva, Guido Viscardi, Andrea Fin. Near‐Infrared Squaraine Dyes as Bright Fluorescent Probes: A Structure–Activity Photophysical Investigation in Liposomes. European Journal of Organic Chemistry 2022, 2022 (37) https://doi.org/10.1002/ejoc.202200833
    19. Taras Sych, Kandice R. Levental, Erdinc Sezgin. Lipid–Protein Interactions in Plasma Membrane Organization and Function. Annual Review of Biophysics 2022, 51 (1) , 135-156. https://doi.org/10.1146/annurev-biophys-090721-072718
    20. Sébastien Jenni, Kévin Renault, Garance Dejouy, Sylvain Debieu, Myriam Laly, Anthony Romieu. In Situ Synthesis of Phenoxazine Dyes in Water: Application for “Turn‐On” Fluorogenic and Chromogenic Detection of Nitric Oxide**. ChemPhotoChem 2022, 6 (5) https://doi.org/10.1002/cptc.202100268

    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2021, 16, 4, 651–660
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschembio.0c00897
    Published March 18, 2021
    Copyright © 2021 American Chemical Society

    Article Views

    2731

    Altmetric

    -

    Citations

    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.