New Insights into Bitopic Orthosteric/Allosteric Ligands of Cannabinoid Receptor Type 2
Rebecca Ferrisi | Beatrice Polini | Caterina Ricardi | Francesca Gado | Kawthar A. Mohamed | Giovanna Baron | Salvatore Faiella | Giulio Poli | Simona Rapposelli | Giuseppe Saccomanni
Experiments in cAMP assays highlighted that only JR22a behaves as a CB2R bitopic (dualsteric) ligand. Further, the results support that JR22a interacts with both orthosteric and allosteric sites (i.e., bitopic), thus reflecting the same bitopic mode of orthosteric/allosteric interaction previously established for the CB2R heterobivalent bitopic ligand FD22a [10]. Computational Studies Starting from our previous definition of the potential allosteric binding site of CB2R and from docking results obtained for the compounds of the FD series [10], we conducted a computational study with the aim of validating the binding pose of our bitopic compounds in CB2R and adding new details on the structure-activity relationship for the bitopic behavior of our CB2R ligands. [Google Scholar] [CrossRef] [PubMed] [Green Version] Valant, C.; Sexton, P.M.; Christopoulos, A. Orthosteric/allosteric bitopic ligands: Going hybrid at GPCRs. Bitopic orthosteric/allosteric ligands of g protein-coupled receptors.