Development of novel near-infrared GFP chromophore-based fluorescent probes for imaging of amyloid-β plaque and viscosity

Development of novel near-infrared GFP chromophore-based fluorescent probes for imaging of amyloid-β plaque and viscosity
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开发新型近红外 GFP 发色团荧光探针,用于淀粉样蛋白-β 斑块和粘度成像

DOI:
10.1016/j.snb.2022.132648
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发表时间:
2022-09
期刊:
Sensors and Actuators B: Chemical
影响因子:
--
通讯作者:
Jinwu Yan
Jinwu Yan
中科院分区:
其他
文献类型:
--
作者:
Yuhui Guo;Huaxiang Leng;Qingxiu Chen;Junyi Su;Wen-jing Shi;Chunli Xia;Lei Zhang;Jinwu Yan

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阿尔茨海默病(Alzheimer's disease,AD)与β淀粉样蛋白(amyloid β,Aβ)异常沉积和斑块形成密切相关。绿色荧光蛋白(GFP)具有高质量的仿生荧光团骨架,在生物医学诊断中得到了广泛的研究。然而,由于内源性物质的吸收、散射和自发荧光,其激发和发射时间很短,因此其在完整动物中的应用受到很大限制。通过对GFP发色团的芳香环和咪唑啉酮环之间的双键桥进行π-延伸,CX 1的发射光谱达到了近红外窗口(702 nm以上),与Aβ聚集体的亲和力明显提高,有效地避免了短激发和短发射对体内成像的限制,对Aβ斑块表现出更高的选择性和信噪比。在Aβ聚集体的疏水空腔中或粘度增加时,由于扭曲的分子内电荷转移受到抑制,CX 1的自由旋转受到有效限制,荧光发射显著增加。此外,CX 1还能清晰地显示转基因小鼠脑内Aβ聚集体和活细胞内粘度的变化,可作为监测AD病理过程的有效工具。
Alzheimer's disease (AD) is closely associated with abnormal deposition of amyloid β (Aβ) peptides and formation of plaques. Green fluorescent protein (GFP) chromophores with a high-quality biomimetic fluorophore skeleton, have been extensively explored in biomedical diagnosis. However, its applications in intact animals were highly limited due to their short excitations and emissions owing to the absorption, scattering and auto-fluorescence by endogenous substances. In this work, through π-extension of the double bond bridge between the aromatic and imidazolidinone rings of the GFP chromophore, the emission ofCX1reached NIR window (over 702 nm) and what’s more interesting, the affinity ofCX1with Aβ aggregates was obviously improved.CX1effectively avoided the limitin vivoimaging due to short excitation and emission and showed higher selectivity and signal-to-noise ratio towards Aβ plaques. In the hydrophobic cavity of Aβ aggregates or increased viscosity, the free rotation ofCX1was efficiently limited due to inhibition of twisted intramolecular charge transfer and thus the fluorescence emission exhibited a significant increase. Furthermore,CX1can clearly image Aβ aggregates in the brain of transgenic mice and viscosity in living cells, which could serve as an effective tool for monitoring the pathological process of AD.
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