PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor.

Authors: Dix AV, Conroy JL, George Rosenker KM, Sibley DR, Appella DH.
Publisher/Year: ACS Med. Chem. Lett. 6(4):425-9.
Pub Med ID/Journal ID: PMID:25893044

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.