"Photo-Adrenalines": Photoswitchable β 2 -Adrenergic Receptor Agonists as Molecular Probes for the Study of Spatiotemporal Adrenergic Signaling.
Alexandra SinkHubert GerweHarald HübnerValérie Boivin-JahnsJulia FenderKristina LorenzPeter GmeinerMichael DeckerPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2024)
β 2 -adrenergic receptor (β 2 -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 β 2 -AR remain vastly elusive, we developed tools for this investigation with high temporal and spatial resolution. Several photoswitchable β 2 -AR agonists with nanomolar activity were synthesized. The most potent agonist for β 2 -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.
Keyphrases
- chronic obstructive pulmonary disease
- lung function
- single molecule
- type diabetes
- induced apoptosis
- heart failure
- cardiovascular disease
- papillary thyroid
- gene expression
- small molecule
- cell cycle arrest
- squamous cell carcinoma
- atrial fibrillation
- oxidative stress
- glycemic control
- cystic fibrosis
- fluorescence imaging
- metabolic syndrome
- living cells
- air pollution
- smoking cessation