Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB Receptor
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 CB receptor. These compounds selectively target CB versus CB recept...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:238561 |
| Acceso en línea: | https://ddd.uab.cat/record/238561 https://dx.doi.org/urn:doi:10.1002/chem.202003389 |
| Access Level: | acceso abierto |
| Palabra clave: | Bitopic ligands CB2 cannabinoid G protein-coupled receptors Molecular dynamics Site-directed mutagenesis |
| Sumario: | 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 CB receptor. These compounds selectively target CB versus CB receptors. Their binding mode was studied by molecular dynamic simulations and site-directed mutagenesis. Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in GPCR pharmacology. We present herein the design, synthesis and functional characterization of the first bitopic ligands for the CB receptor. Molecular understanding of the binding mode was guided by molecular dynamic simulations and site-directed mutagenesis. |
|---|