基于肽核酸的多价支架激活多巴胺D2受体。
PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor.
作者信息
Dix Andrew V, Conroy Jennie L, George Rosenker Kara M, Sibley David R, Appella Daniel H
机构信息
Laboratory of Bioorganic Chemistry, NIDDK, and Molecular Neuropharmacology Section, NINDS, National Institutes of Health , Bethesda, Maryland 20892, United States.
出版信息
ACS Med Chem Lett. 2015 Mar 13;6(4):425-9. doi: 10.1021/ml500478m. eCollection 2015 Apr 9.
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.
摘要
肽核酸支架是一种用于探究配体与膜受体结合的多价效应的有前景的工具。多巴胺D2受体（D2R）是一类G蛋白偶联受体（GPCR），这些受体的高阶结构形成与几种神经疾病的进展有关。在本信函中，我们描述了带有已知D2R激动剂（±）-PPHT的配体修饰的肽核酸文库的合成。评估了每个构建体的D2R活性，并对多价效应进行了评价。
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