title: PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor.
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.
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, and Molecular Neuropharmacology Section, NINDS, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Dix
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, and Molecular Neuropharmacology Section, NINDS, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Jennie L
authors.initials: JL
authors.lastname: Conroy
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, and Molecular Neuropharmacology Section, NINDS, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Kara M
authors.initials: KM
authors.lastname: George Rosenker
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, and Molecular Neuropharmacology Section, NINDS, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Sibley
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, and Molecular Neuropharmacology Section, NINDS, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Appella
keywords: Peptide nucleic acid; dopamine D2 receptor; multivalent display; self-assembly