A Photoswitchable Ligand Targeting the β1 -Adrenoceptor Enables Light-Control of the Cardiac Rhythm
Catecholamine-triggered β-adrenoceptor (β-AR) signaling is essential for the correct functioning of the heart. Although both β1 - and β2 -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β1 -AR have proven this receptor as the main target for the therapeutic effects of beta b...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/274758 |
| Acceso en línea: | http://hdl.handle.net/10261/274758 |
| Access Level: | acceso abierto |
| Palabra clave: | Photochromism Catena, Juan Lorenzo Azobenzene Beta-1 Adrenoceptors Drug Design Light-Regulated Ligands |
| Sumario: | Catecholamine-triggered β-adrenoceptor (β-AR) signaling is essential for the correct functioning of the heart. Although both β1 - and β2 -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β1 -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy for the light-control of β1 -AR activation by means of photoswitchable drugs with a high level of β1 -/β2 -AR selectivity. All reported molecules allow for an efficient real-time optical control of receptor function in vitro. Moreover, using confocal microscopy we demonstrate that the binding of our best hit, pAzo-2, can be reversibly photocontrolled. Strikingly, pAzo-2 also enables a dynamic cardiac rhythm management on living zebrafish larvae using light, thus highlighting the therapeutic and research potential of the developed photoswitches. Overall, this work provides the first proof of precise control of the therapeutic target β1 -AR in native environments using light. |
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