Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB2 Receptor*

Abstract

Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB₂ receptor. These compounds selectively target CB₂ versus CB₁ receptors. Their binding mode was studied by molecular dynamic simulations and site-directed mutagenesis.

Keywords: CB2 cannabinoid; G protein-coupled receptors; bitopic ligands; molecular dynamics; site-directed mutagenesis.