Detection of 伪-Synuclein Amyloidogenic Aggregates in Vitro and in Cells using Light-Switching Dipyridophenazine Ruthenium(II) Complexes

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• 作者：Nathan P. Cook ; Kiri Kilpatrick ; Laura Segatori ; Angel A. Mart铆
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：December 26, 2012
• 年：2012
• 卷：134
• 期：51
• 页码：20776-20782
• 全文大小：406K
• 年卷期：v.134,no.51(December 26, 2012)
• ISSN：1520-5126

文摘

Protein aggregation is the hallmark of a number of neurodegenerative diseases including Parkinson鈥檚 and Huntington鈥檚 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鈥搑esponsive compounds suitable to cellular studies, we present a ruthenium(II) dipyridophenazine derivative, [Ru(phen)₂dppz]²⁺ (phen =1,10-phenanthroline, dppz = dipyrido[3,2-a:2鈥?3鈥?c]phenazine), to study aggregation of 伪-synuclein (伪S), which is associated with the development of Parkinson鈥檚 disease. We demonstrated the use of [Ru(phen)₂dppz]²⁺ to monitor 伪S fibril formation in real-time and to detect and quantify 伪S aggregates in neuroglioma cells, thereby providing a novel molecular tool to study protein deposition diseases in vitro and in vivo.