Current Advances in Allosteric Modulation of Muscarinic Receptors

0523829 - FGÚ 2021 RIV CH eng J - Článek v odborném periodiku
Jakubík, Jan - El-Fakahany, E. E.
Current Advances in Allosteric Modulation of Muscarinic Receptors.
Biomolecules. Roč. 10, č. 2 (2020), č. článku 325. E-ISSN 2218-273X
Grant CEP: GA ČR(CZ) GA19-05318S
Institucionální podpora: RVO:67985823
Klíčová slova: acetylcholine * muscarinic receptors * allosteric modulation
Obor OECD: Physiology (including cytology)
Impakt faktor: 4.879, rok: 2020
Způsob publikování: Open access
https://doi.org/10.3390/biom10020325

Allosteric modulators are ligands that bind to a site on the receptor that is spatially separated from the orthosteric binding site for the endogenous neurotransmitter. Allosteric modulators modulate the binding affinity, potency, and efficacy of orthosteric ligands. Muscarinic acetylcholine receptors are prototypical allosterically-modulated G-protein-coupled receptors. They are a potential therapeutic target for the treatment of psychiatric, neurologic, and internal diseases like schizophrenia, Alzheimer's disease, Huntington disease, type 2 diabetes, or chronic pulmonary obstruction. Here, we reviewed the progress made during the last decade in our understanding of their mechanisms of binding, allosteric modulation, and in vivo actions in order to understand the translational impact of studying this important class of pharmacological agents. We overviewed newly developed allosteric modulators of muscarinic receptors as well as new spin-off ideas like bitopic ligands combining allosteric and orthosteric moieties and photo-switchable ligands based on bitopic agents.
Trvalý link: http://hdl.handle.net/11104/0308111