Synthesis and characterization of high-affinity 4, 4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human β-adrenoceptors
he growing practice of exploiting noninvasive fluorescence-based techniques to study G protein-coupled receptor pharmacology at the single cell and single molecule level demands the availability of high-quality fluorescent ligands. To this end, this study evaluated a new series of red-emitting ligan...
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| Format: | Article |
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American Chemical Society
2011
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| Online Access: | https://eprints.nottingham.ac.uk/2734/ |
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| author | Baker, Jillian G. Adams, Luke A. Salchow, Karolina Mistry, Shailesh N. Middleton, Richard J. Hill, Stephen J. Kellam, Barrie |
| author_facet | Baker, Jillian G. Adams, Luke A. Salchow, Karolina Mistry, Shailesh N. Middleton, Richard J. Hill, Stephen J. Kellam, Barrie |
| author_sort | Baker, Jillian G. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | he growing practice of exploiting noninvasive fluorescence-based techniques to study G protein-coupled receptor pharmacology at the single cell and single molecule level demands the availability of high-quality fluorescent ligands. To this end, this study evaluated a new series of red-emitting ligands for the human β-adrenoceptor family. Upon the basis of the orthosteric ligands propranolol, alprenolol, and pindolol, the synthesized linker-modified congeners were coupled to the commercially available fluorophore BODIPY 630/650-X. This yielded high-affinity β-adrenoceptor fluorescent ligands for both the propranolol and alprenolol derivatives; however, the pindolol-based products displayed lower affinity. A fluorescent diethylene glycol linked propranolol derivative (18a) had the highest affinity (log KD of −9.53 and −8.46 as an antagonist of functional β2- and β1-mediated responses, respectively). Imaging studies with this compound further confirmed that it can be employed to selectively label the human β2-adrenoceptor in single living cells, with receptor-associated binding prevented by preincubation with the nonfluorescent β2-selective antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118551) (J. Cardiovasc. Pharmacol.1983, 5, 430–437.) |
| first_indexed | 2025-11-14T18:19:21Z |
| format | Article |
| id | nottingham-2734 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:19:21Z |
| publishDate | 2011 |
| publisher | American Chemical Society |
| recordtype | eprints |
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| spelling | nottingham-27342020-05-04T16:30:58Z https://eprints.nottingham.ac.uk/2734/ Synthesis and characterization of high-affinity 4, 4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human β-adrenoceptors Baker, Jillian G. Adams, Luke A. Salchow, Karolina Mistry, Shailesh N. Middleton, Richard J. Hill, Stephen J. Kellam, Barrie he growing practice of exploiting noninvasive fluorescence-based techniques to study G protein-coupled receptor pharmacology at the single cell and single molecule level demands the availability of high-quality fluorescent ligands. To this end, this study evaluated a new series of red-emitting ligands for the human β-adrenoceptor family. Upon the basis of the orthosteric ligands propranolol, alprenolol, and pindolol, the synthesized linker-modified congeners were coupled to the commercially available fluorophore BODIPY 630/650-X. This yielded high-affinity β-adrenoceptor fluorescent ligands for both the propranolol and alprenolol derivatives; however, the pindolol-based products displayed lower affinity. A fluorescent diethylene glycol linked propranolol derivative (18a) had the highest affinity (log KD of −9.53 and −8.46 as an antagonist of functional β2- and β1-mediated responses, respectively). Imaging studies with this compound further confirmed that it can be employed to selectively label the human β2-adrenoceptor in single living cells, with receptor-associated binding prevented by preincubation with the nonfluorescent β2-selective antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118551) (J. Cardiovasc. Pharmacol.1983, 5, 430–437.) American Chemical Society 2011-08-29 Article PeerReviewed Baker, Jillian G., Adams, Luke A., Salchow, Karolina, Mistry, Shailesh N., Middleton, Richard J., Hill, Stephen J. and Kellam, Barrie (2011) Synthesis and characterization of high-affinity 4, 4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human β-adrenoceptors. Journal of Medicinal Chemistry, 54 (19). pp. 6874-6887. ISSN 0022-2623 http://pubs.acs.org/doi/abs/10.1021/jm2008562?prevSearch=%255BContrib%253A%2BJillian%2BBaker%255D&searchHistoryKey= doi:10.1021/jm2008562 doi:10.1021/jm2008562 |
| spellingShingle | Baker, Jillian G. Adams, Luke A. Salchow, Karolina Mistry, Shailesh N. Middleton, Richard J. Hill, Stephen J. Kellam, Barrie Synthesis and characterization of high-affinity 4, 4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human β-adrenoceptors |
| title | Synthesis and characterization of high-affinity 4,
4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent
ligands for human β-adrenoceptors |
| title_full | Synthesis and characterization of high-affinity 4,
4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent
ligands for human β-adrenoceptors |
| title_fullStr | Synthesis and characterization of high-affinity 4,
4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent
ligands for human β-adrenoceptors |
| title_full_unstemmed | Synthesis and characterization of high-affinity 4,
4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent
ligands for human β-adrenoceptors |
| title_short | Synthesis and characterization of high-affinity 4,
4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent
ligands for human β-adrenoceptors |
| title_sort | synthesis and characterization of high-affinity 4,
4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent
ligands for human β-adrenoceptors |
| url | https://eprints.nottingham.ac.uk/2734/ https://eprints.nottingham.ac.uk/2734/ https://eprints.nottingham.ac.uk/2734/ |