Department of Chemistry, Rice University, Houston, Texas 77005, USA.
J Am Chem Soc. 2012 Dec 26;134(51):20776-82. doi: 10.1021/ja3100287. Epub 2012 Dec 14.
Protein aggregation is the hallmark of a number of neurodegenerative diseases including Parkinson's and Huntington's diseases. There is a significant interest in understanding the molecular mechanisms involved in the self-association and fibrillization of monomeric soluble proteins into insoluble deposits in vivo and in vitro. Probes with novel properties, such as red-shifted emission, large Stokes shifts, and high photostability, are desirable for a variety of protein aggregation studies. To respond to the increasing need for aggregation-responsive compounds suitable to cellular studies, we present a ruthenium(II) dipyridophenazine derivative, Ru(phen)(2)dppz (phen =1,10-phenanthroline, dppz = dipyrido[3,2-a:2'.3'-c]phenazine), to study aggregation of α-synuclein (αS), which is associated with the development of Parkinson's disease. We demonstrated the use of Ru(phen)(2)dppz to monitor αS fibril formation in real-time and to detect and quantify αS aggregates in neuroglioma cells, thereby providing a novel molecular tool to study protein deposition diseases in vitro and in vivo.
蛋白质聚集是许多神经退行性疾病的标志，包括帕金森病和亨廷顿病。人们对理解单体可溶性蛋白质在体内和体外自缔合和纤维化形成不溶性沉积物的分子机制非常感兴趣。具有新型特性的探针，如红移发射、大斯托克斯位移和高光稳定性，是各种蛋白质聚集研究所需的。为了满足对适合细胞研究的聚集反应性化合物的需求不断增加，我们提出了一种钌（II）二吡啶并吩嗪衍生物[Ru（phen）（2）dppz]（2+）（phen=1,10-邻菲咯啉，dppz=二吡啶并[3,2-a:2'.3'-c]吩嗪），以研究与帕金森病发展相关的α-突触核蛋白（αS）的聚集。我们证明了[Ru（phen）（2）dppz]（2+）可用于实时监测αS 纤维形成，并检测和定量神经胶质瘤细胞中的αS 聚集体，从而提供了一种新的分子工具，用于研究体内和体外的蛋白质沉积疾病。
