“Photo-Adrenalines”: Photoswitchable β2-Adrenergic Receptor Agonists as Molecular Probes for the Study of Spatiotemporal Adrenergic Signaling

Abstract

β2-adrenergic receptor (β2-AR) agonists are used for the treatment of asthma and chronic obstructive pulmonary disease, but also play a role in other complex disorders including cancer, diabetes and heart diseases. As the cellular and molecular mechanisms in various cells and tissues of the β2-AR remain vastly elusive, we developed tools for this investigation with high temporal and spatial resolution. Several photoswitchable β2-AR agonists with nanomolar activity were synthesized. The most potent agonist for β2-AR with reasonable switching is a one-digit nanomolar active, trans-on arylazopyrazole-based adrenaline derivative and comprises valuable photopharmacological properties for further biological studies with high structural accordance to the native ligand adrenaline.