Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications in Single-Molecule Microscopy of Wild-Type Receptors

Drakopoulos A, Koszegi Z, Seier K, Hübner H, Maurel D, Sounier R, Granier S, Gmeiner P, Calebiro D, Decker M (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Journal of Medicinal Chemistry American Chemical Society

Book Volume: 67

Pages Range: 12618-12631

Journal Issue: 15

DOI: 10.1021/acs.jmedchem.4c00627

Abstract

The delta opioid receptor (δOR or DOR) is a G protein-coupled receptor (GPCR) showing a promising profile as a drug target for nociception and analgesia. Herein, we design and synthesize new fluorescent antagonist probes with high δOR selectivity that are ideally suited for single-molecule microscopy (SMM) applications in unmodified, untagged receptors. Using our new probes, we investigated wild-type δOR localization and mobility at low physiological receptor densities for the first time. Furthermore, we investigate the potential formation of δOR homodimers, as such a receptor organization might exhibit distinct pharmacological activity, potentially paving the way for innovative pharmacological therapies. Our findings indicate that the majority of δORs labeled with these probes exist as freely diffusing monomers on the cell surface in a simple cell model. This discovery advances our understanding of OR behavior and offers potential implications for future therapeutic research.

Authors with CRIS profile

Harald Hübner Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie

Additional Organisation(s)

FAU Forschungszentrum Neue Wirkstoffe (FAU NeW)

Involved external institutions

University of Montpellier / Université Montpellier FR France (FR) Julius-Maximilians-Universität Würzburg DE Germany (DE) University of Birmingham GB United Kingdom (GB)

How to cite

APA:

Drakopoulos, A., Koszegi, Z., Seier, K., Hübner, H., Maurel, D., Sounier, R.,... Decker, M. (2024). Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications in Single-Molecule Microscopy of Wild-Type Receptors. Journal of Medicinal Chemistry, 67(15), 12618-12631. https://doi.org/10.1021/acs.jmedchem.4c00627

MLA:

Drakopoulos, Antonios, et al. "Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications in Single-Molecule Microscopy of Wild-Type Receptors." Journal of Medicinal Chemistry 67.15 (2024): 12618-12631.

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