PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor

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 associ...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2015-04, Vol.6 (4), p.425-429
Main Authors: Dix, Andrew V, Conroy, Jennie L, George Rosenker, Kara M, Sibley, David R, Appella, Daniel H
Format: Article
Language:English
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Letter
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Summary: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.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml500478m