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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本文引用的文献
1
Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors.
Angew Chem Int Ed Engl. 1998 Nov 2;37(20):2754-2794. doi: 10.1002/(SICI)1521-3773(19981102)37:20<2754::AID-ANIE2754>3.0.CO;2-3.
2
Dopamine receptors and Parkinson's disease.
Int J Med Chem. 2011;2011:403039. doi: 10.1155/2011/403039. Epub 2011 Jun 13.
3
Double-clicking peptides onto phosphorothioate oligonucleotides: combining two proapoptotic agents in one molecule.
Angew Chem Int Ed Engl. 2014 Sep 22;53(39):10504-9. doi: 10.1002/anie.201406674. Epub 2014 Aug 19.
4
Programmable nanoscaffolds that control ligand display to a G-protein-coupled receptor in membranes to allow dissection of multivalent effects.
J Am Chem Soc. 2014 Sep 3;136(35):12296-303. doi: 10.1021/ja504288s. Epub 2014 Aug 25.
5
Dopamine D₁-D₂ receptor heteromer regulates signaling cascades involved in addiction: potential relevance to adolescent drug susceptibility.
Dev Neurosci. 2014;36(3-4):287-96. doi: 10.1159/000360158. Epub 2014 May 8.
6
Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor.
Mol Pharmacol. 2014 Jul;86(1):96-105. doi: 10.1124/mol.113.090563. Epub 2014 Apr 22.
7
Nucleic acid-programmed assemblies: translating instruction into function in chemical biology.
Chimia (Aarau). 2013;67(5):340-8. doi: 10.2533/chimia.2013.340.
8
Heteromeric dopamine receptor signaling complexes: emerging neurobiology and disease relevance.
Neuropsychopharmacology. 2014 Jan;39(1):156-68. doi: 10.1038/npp.2013.148. Epub 2013 Jun 18.
9
Class A G-protein-coupled receptor (GPCR) dimers and bivalent ligands.
J Med Chem. 2013 Sep 12;56(17):6542-59. doi: 10.1021/jm4004335. Epub 2013 Jun 4.
10
Novel bivalent ligands for D2/D3 dopamine receptors: Significant co-operative gain in D2 affinity and potency.
ACS Med Chem Lett. 2012 Oct 26;3(12):991-996. doi: 10.1021/ml3002117.
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