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Study of the cross-talk between the dopamine D2-like receptors and the μ opioid receptor M. Qian1,2, K. Van Craenenbroeck2, S. Van Calenbergh1* 1. Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Gent 2. L-GEST, Faculty of Sciences, Ghent University, Proeftuinstraat 86, B-9000 Gent G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins. A vastly unexplored functional property of GPCRs concerns their propensity to engage in oligomeric assemblies involving two or more GPCRs to form homo- and heterodimers, as well as higher order multimers. Such GPCR dimers and in particular, heterodimers, can have a profound impact on signaling. Dopamine D2type and μ opioid receptors, two GPCRs expressed in the brain, play a major role in pain and addiction. In this project we describe the synthesis of bivalent ligands for μ Opioid Receptor-D2-like Receptor (μOR-D2-likeR) to further study this receptor interaction. Known ligands for both GPCRs were conjugated via linkers of different length and composition. The final step in the conjugation consists of a so-called click reaction. We determined the affinity of the bivalent ligands for μOR-D2-likeR dimers. In addition, functional assays (e.g. the MAPK-P assay) were used to asses signal transduction.