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PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor
Andrew V Dix1, Jennie L Conroy1, Kara M George Rosenker1
1Laboratory of Bioorganic Chemistry, NIDDK, and Molecular Neuropharmacology Section, NINDS, National Institutes of Health , Bethesda, Maryland 20892, United States.
Abstract:
Peptide nucleic acid scaffolds represent a promising tool to interrogate the multivalent effects of ligand binding to a membrane receptor. Dopamine D2 receptors (D2R) are a class of G-protein coupled receptors (GPCRs), and the formation of higher-ordered structures of these receptors has been associated with the progression of several neurological diseases. In this Letter, we describe the synthesis of a library of ligand-modified PNAs bearing a known D2R agonist, (±)-PPHT. The D2R activity for each construct was assessed, and the multivalent effects were evaluated.
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