Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor
Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evalua...
| Main Authors: | , , , , , , |
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| Format: | Article |
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American Chemical Society
2015
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| Online Access: | https://eprints.nottingham.ac.uk/50604/ |
| _version_ | 1848798294195568640 |
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| author | Schembri, Luke S. Stoddart, Leigh A. Briddon, Stephen J. Kellam, Barrie Canals, Meritxell Graham, Bim Scammells, Peter J. |
| author_facet | Schembri, Luke S. Stoddart, Leigh A. Briddon, Stephen J. Kellam, Barrie Canals, Meritxell Graham, Bim Scammells, Peter J. |
| author_sort | Schembri, Luke S. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evaluation of fluorescent probes for the opioid receptors, for which relatively few non-peptidic fluorescent probes currently exist. The known μ-opioid receptor (MOR) partial agonist, buprenorphine, was structurally elaborated to include an amidoalkylamine linker moiety that was coupled with a range of fluorophores to afford new fluorescent probes. All compounds proved to be selective MOR antagonists. Confocal fluorescence microscopy studies revealed that the probe incorporating a sulfonated cyanine-5 fluorophore was the most appropriate for imaging studies. This ligand was subsequently employed in an automated fluorescence-based competition binding assay, allowing the pKi values of several well-known opioid ligands to be determined. Thus, this new probe will prove useful in future studies of MOR receptor pharmacology. |
| first_indexed | 2025-11-14T20:17:29Z |
| format | Article |
| id | nottingham-50604 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:17:29Z |
| publishDate | 2015 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-506042020-05-04T17:28:17Z https://eprints.nottingham.ac.uk/50604/ Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor Schembri, Luke S. Stoddart, Leigh A. Briddon, Stephen J. Kellam, Barrie Canals, Meritxell Graham, Bim Scammells, Peter J. Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evaluation of fluorescent probes for the opioid receptors, for which relatively few non-peptidic fluorescent probes currently exist. The known μ-opioid receptor (MOR) partial agonist, buprenorphine, was structurally elaborated to include an amidoalkylamine linker moiety that was coupled with a range of fluorophores to afford new fluorescent probes. All compounds proved to be selective MOR antagonists. Confocal fluorescence microscopy studies revealed that the probe incorporating a sulfonated cyanine-5 fluorophore was the most appropriate for imaging studies. This ligand was subsequently employed in an automated fluorescence-based competition binding assay, allowing the pKi values of several well-known opioid ligands to be determined. Thus, this new probe will prove useful in future studies of MOR receptor pharmacology. American Chemical Society 2015-12-03 Article PeerReviewed Schembri, Luke S., Stoddart, Leigh A., Briddon, Stephen J., Kellam, Barrie, Canals, Meritxell, Graham, Bim and Scammells, Peter J. (2015) Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor. Journal of Medicinal Chemistry, 58 (24). pp. 9754-9767. ISSN 1520-4804 https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b01664 doi:10.1021/acs.jmedchem.5b01664 doi:10.1021/acs.jmedchem.5b01664 |
| spellingShingle | Schembri, Luke S. Stoddart, Leigh A. Briddon, Stephen J. Kellam, Barrie Canals, Meritxell Graham, Bim Scammells, Peter J. Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor |
| title | Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor |
| title_full | Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor |
| title_fullStr | Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor |
| title_full_unstemmed | Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor |
| title_short | Synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor |
| title_sort | synthesis, biological evaluation, and utility of fluorescent ligands targeting the μ-opioid receptor |
| url | https://eprints.nottingham.ac.uk/50604/ https://eprints.nottingham.ac.uk/50604/ https://eprints.nottingham.ac.uk/50604/ |