Exploring the Effect of Aliphatic Substituents on Aryl Cyano Amides on Enhancement of Fluorescence upon Binding to Amyloid-β Aggregates.
Exploring the Effect of Aliphatic Substituents on Aryl Cyano Amides on Enhancement of Fluorescence upon Binding to Amyloid-β Aggregates.
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DOI：
10.1021/acschemneuro.1c00334
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发表时间：
2021-08-04
影响因子：
5
通讯作者：
Yang, Jerry
中科院分区：
文献类型：
--
作者：
Ehrlich, Rachel S.;Shiao, Alexander L.;Li, Meihan;Teppang, Kristine L.;Jeoung, Kun Yong;Theodorakis, Emmanuel A.;Yang, Jerry
淀粉样蛋白-β (a β)肽自组装成淀粉样蛋白聚集体是阿尔茨海默病的病理标志。我们之前报道了一种荧光芳基氰酰胺（Aryl Cyano Amide， ARCAM）探针，该探针在溶液和神经元组织中与a β聚集体结合时显示出荧光发射的增加。在这里，我们研究了引入小脂肪取代基对溶液中游离和与聚集的a - β结合的ARCAM光谱性质的影响。我们发现，在这些荧光团上引入旨在阻碍电子供体和受体之间键旋转的取代基，会影响探针在无淀粉样蛋白溶液中荧光发射的总体亮度，但这些探针在含淀粉样蛋白溶液中的相对荧光增强取决于取代基在ARCAM支架上的位置。我们还观察到通过引入供电子或吸电子取代基来调节这些探针的激发或发射波长的能力，这些取代基可能会影响光激发所需的能量或光激发态的稳定性。这些研究揭示了开发基于arcam的荧光a β结合探针的新设计原则，与背景和可调光谱特性相比，该探针具有增强的荧光信号，这可能导致改进的化学工具，以帮助诊断淀粉样蛋白相关的神经退行性疾病。
The self-assembly of amyloid-β (Aβ) peptides into amyloid aggregates is a pathological hallmark of Alzheimer’s Disease. We previously reported a fluorescent Aryl Cyano Amide (ARCAM) probe that exhibits an increase in fluorescence emission upon binding to Aβ aggregates in solution and in neuronal tissue. Here, we investigate the effect of introducing small aliphatic substituents on the spectroscopic properties of ARCAM both free in solution and when bound to aggregated Aβ. We found that introducing substituents designed to hinder the rotation of bonds between the electron donor and acceptor on these fluorophores can affect the overall brightness of fluorescence emission of the probes in amyloid-free solutions, but the relative fluorescence enhancement of these probes in amyloid-containing solutions is dependent on the location of the substituents on the ARCAM scaffold. We also observed the capability to tune the excitation or emission wavelength of these probes by introducing electron-donating or -withdrawing substituents that putatively affect either the energy required for photoexcitation or the stability of the photoexcited state. These studies reveal new design principles for developing ARCAM-based fluorescent Aβ-binding probes with an enhanced fluorescence signal compared to background and tunable spectroscopic properties, which may lead to improved chemical tools for aiding in the diagnosis of amyloid-associated neurodegenerative diseases.
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影响因子：
5
作者：
Guan Y;Cao KJ;Cantlon A;Elbel K;Theodorakis EA;Walsh DM;Yang J;Shah JV
通讯作者：
Shah JV
影响因子：
5
作者：
Cifelli, Jessica L.;Capule, Christina C.;Yang, Jerry
通讯作者：
Yang, Jerry
影响因子：
3.7
作者：
Manook A;Yousefi BH;Willuweit A;Platzer S;Reder S;Voss A;Huisman M;Settles M;Neff F;Velden J;Schoor M;von der Kammer H;Wester HJ;Schwaiger M;Henriksen G;Drzezga A
通讯作者：
Drzezga A
影响因子：
14
作者：
通讯作者：
--
影响因子：
3.4
作者：
Kerbage C;Sadowsky CH;Jennings D;Cagle GD;Hartung PD
通讯作者：
Hartung PD