One for the Price of Two
Are Bivalent Ligands Targeting Cannabinoid Receptor Dimers Capable of Simultaneously Binding to both Receptors?
Trends Pharmacol Sci
; 37(5): 353-363, 2016 05.
Article
em En
| MEDLINE
| ID: mdl-26917061
ABSTRACT
Bivalent ligands bridging two G-protein-coupled receptors (GPCRs) provide valuable pharmacological tools to target oligomers. The success of therapeutically targeting the cannabinoid CB1 receptor has been limited, in part due to its widespread neuronal distribution. Therefore, CB1 ligands targeting oligomers that exhibit restricted distribution or altered pharmacology are highly desirable, and several bivalent ligands containing a CB1 pharmacophore have been reported. Bivalent ligand action presumes that the ligand simultaneously binds to both receptors within the dimeric complex. However, based on the current understanding of CB1 ligand binding, existing bivalent ligands are too short to bind both receptors simultaneously. However, ligands with longer linkers may not be the solution, because evidence suggests that ligands enter CB1 through the lipid bilayer and, thus, linkers are unlikely to exit the receptor through its external face. Thus, the entire premise of designing bivalent ligands targeting CB1 must be revisited.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Canabinoides
/
Agonistas de Receptores de Canabinoides
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article