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Optical control of the β2-adrenergic receptor with opto-prop-2: A cis-active azobenzene analog of propranolol

Bosma, Reggie; Dijon, Nicola C.; Zheng, Yang; Schihada, Hannes; Hauwert, Niels J.; Shi, Shuang; Arimont, Marta; Riemens, Rick; Custers, Hans; van de Stolpe, Andrea; Vischer, Henry F.; Wijtmans, Maikel; Holliday, Nicholas D.; Kuster, Diederik W.D.; Leurs, Rob


Reggie Bosma

Nicola C. Dijon

Yang Zheng

Hannes Schihada

Niels J. Hauwert

Shuang Shi

Marta Arimont

Rick Riemens

Hans Custers

Andrea van de Stolpe

Henry F. Vischer

Maikel Wijtmans

Diederik W.D. Kuster

Rob Leurs


In this study, we synthesized and evaluated new photoswitchable ligands for the beta-adrenergic receptors β1-AR and β2-AR, applying an azologization strategy to the first-generation beta-blocker propranolol. The resulting compounds (Opto-prop-1, -2, -3) have good photochemical properties with high levels of light-induced trans-cis isomerization (>94%) and good thermal stability (t1/2 > 10 days) of the resulting cis-isomer in an aqueous buffer. Upon illumination with 360-nm light to PSScis, large differences in binding affinities were observed for photoswitchable compounds at β1-AR as well as β2-AR. Notably, Opto-prop-2 (VUF17062) showed one of the largest optical shifts in binding affinities at the β2-AR (587-fold, cis-active), as recorded so far for photoswitches of G protein-coupled receptors. We finally show the broad utility of Opto-prop-2 as a light-dependent competitive antagonist of the β2-AR as shown with a conformational β2-AR sensor, by the recruitment of downstream effector proteins and functional modulation of isolated adult rat cardiomyocytes.


Bosma, R., Dijon, N. C., Zheng, Y., Schihada, H., Hauwert, N. J., Shi, S., …Leurs, R. (2022). Optical control of the β2-adrenergic receptor with opto-prop-2: A cis-active azobenzene analog of propranolol. iScience, 25(9), Article 104882.

Journal Article Type Article
Acceptance Date Aug 2, 2022
Online Publication Date Sep 16, 2022
Publication Date Sep 16, 2022
Deposit Date Sep 28, 2022
Publicly Available Date Oct 4, 2022
Journal iScience
Electronic ISSN 2589-0042
Publisher Cell Press
Peer Reviewed Peer Reviewed
Volume 25
Issue 9
Article Number 104882
Keywords Multidisciplinary
Public URL
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