Lahmy, Ranit and Huebner, Harald and Gmeiner, Peter and Koenig, Burkhard (2024) Covalent and Visible-Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes. CHEMPHOTOCHEM, 8 (7). e202400022. ISSN 2367-0932,
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Isotonitazene belongs to a potent class of mu-opioid receptor (mu OR) ligands, known as nitazenes. The lack of knowledge surrounding this agonist and others in its class has sparked thorough re-investigations. To aid in these investigations, the purportedly covalent yet underexplored nitazene BIT was biochemically re-evaluated in this work, along with a newly synthesized analogue, Iso-BIT. Moreover, in the pursuit of understanding the mechanism, function and interactions of the mu OR, this study involved developing photoswitchable nitazene derivatives as potential probe molecules. Converting known ligands into azo-containing photoswitchable derivatives offers the opportunity to modulate ligand structure with light, allowing for photocontrol of compound activity. While photocontrol of mu OR activity could not be entirely achieved, photophysical evaluation of these 2-benzimidazole azo-arenes revealed a novel photoswitch scaffold that responds to visible light. Furthermore, azo-containing 2 e and 3 e emerged as promising nitazene derivatives that were able to form an exceptionally high fraction of covalent-ligand receptor complexes with wild-type mu OR at physiological pH. Potent synthetic opioids, nitazenes, were converted into photoswitchable derivatives and derivatives containing an isothiocyanate functionality for covalent interaction with the mu-opioid receptor. Photophysical analysis of the resulting 2-benzimidazole azo-arenes revealed a novel photoswitch scaffold that responds to visible light. Importantly, ligands in this series were able to effectively localize and covalently bind to the target receptor at physiological pH. image
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECEPTOR-MEDIATED PHENOMENA; BINDING-SITES; DELTA-OPIATE; AZOBENZENE PHOTOSWITCHES; IRREVERSIBLE LIGANDS; OPTICAL CONTROL; MU-RECEPTOR; GUINEA-PIG; PROBES; BRAIN; covalent; isotonitazene; mu-opioid receptor; G-protein-coupled receptor; photopharmacology |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Jan 2026 10:44 |
| Last Modified: | 13 Jan 2026 10:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64178 |
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