Design and Validation of the First Family of Photo-Activatable Ligands for Melatonin Receptors.

ABSTRACT: Melatonin is a neurohormone released in a circadian manner with peak levels at night. Melatonin mediates its effects mainly through G protein-coupled MT₁ and MT₂ receptors. Drugs acting on melatonin receptors are indicated for circadian rhythm- and sleep-related disorders. Tools to study the activation of these receptors with high temporal resolution are lacking. Here, we synthesized a family of light-activatable caged compounds by attaching o-nitrobenzyl (o-NB) or coumarin photocleavable groups to melatonin indolic nitrogen. All caged compounds showed the expected decrease in binding affinity for MT₁ and MT₂. The o-NB derivative MCS-0382 showed the best uncaging and biological properties, with 250-fold increase in affinity a

SUBMITTER: Somalo-Barranco G 

PROVIDER: S-EPMC9421648 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature