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Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB2 Receptor** |
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| Authors: | Dr. Paula Morales Dr. Gemma Navarro Marc Gómez-Autet Laura Redondo Prof. Dr. Javier Fernández-Ruiz Dr. Laura Pérez-Benito Dr. Arnau Cordomí Prof. Dr. Leonardo Pardo Prof. Dr. Rafael Franco Dr. Nadine Jagerovic |
| Affiliation: | 1. Medicinal Chemistry Institute, Spanish Research Council, Madrid, Spain;2. Department of Biochemistry and Physiology, CIBERNED, Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain;3. Laboratory of Computational Medicine, Biostatistics Unit, Faculty of Medicine, Universitat Autónoma de Barcelona, Barcelona, Spain These authors contributed equally to this work.;4. Department of Biochemistry and Molecular Biology, CIBERNED, IRYCIS, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain;5. Laboratory of Computational Medicine, Biostatistics Unit, Faculty of Medicine, Universitat Autónoma de Barcelona, Barcelona, Spain |
| 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: | bitopic ligands CB2 cannabinoid G protein-coupled receptors molecular dynamics site-directed mutagenesis |