Investigation of inactive state κ opioid receptor homodimerization via single molecule microscopy using new antagonistic fluorescent probes
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
Opioid receptors (ORs) are among the best-studied G protein-coupled receptors due to their involvement in neurological disorders and important role in pain treatment. Contrary to the classical monomeric model, indirect evidence suggests that ORs might form dimers, which could be endowed with a distinct pharmacological profile, and, thus, be targeted to develop innovative pharmacological therapies. However, direct evidence for the spontaneous formation of OR dimers in living cells under physiological conditions is missing. Despite a growing interest in the κ opioid receptor (KOR), KORselective fluorescent probes are particularly scarce in the literature. Herein, we present the first set of fluorescent KOR-selective probes with antagonistic properties. Two of these were employed in single-molecule microscopy (SMM) experiments to investigate KOR homodimerization, localization, and trafficking. Our findings indicate that most KORs labeled with the new fluorescent probes are present as apparently freely diffusing monomers on the surface of a simple cell model.
|Number of pages||14|
|Journal||Journal of Medicinal Chemistry|
|Early online date||11 Mar 2020|
|Publication status||Published - 9 Apr 2020|