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

Chemistry. 2024 Feb 21;30(11):e202303506. doi: 10.1002/chem.202303506. Epub 2024 Jan 11.

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.

Keywords: Agonist; Arylazopyrazole; Azobenzene; Photopharmacology; β-Adrenergic receptor.

MeSH terms

  • Adrenergic Agents*
  • Adrenergic beta-2 Receptor Agonists* / pharmacology
  • Epinephrine / pharmacology
  • Molecular Probes
  • Receptors, Adrenergic, beta-2 / chemistry
  • Signal Transduction

Substances

  • Adrenergic Agents
  • Adrenergic beta-2 Receptor Agonists
  • Molecular Probes
  • Receptors, Adrenergic, beta-2
  • Epinephrine