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Unfolding the Role of a Flavone-Based Fluorescent Antioxidant towards the Misfolding of Amyloid Proteins: An Endeavour to Probe Amyloid Aggregation
The Journal of Physical Chemistry B ( IF 3.3 ) Pub Date : 2020-11-23 , DOI: 10.1021/acs.jpcb.0c08729
Abhijit Karmakar 1 , Tamanna Mallick 1 , Chandrani Fouzder 2 , Alpana Mukhuty 2 , Samiran Mondal 3 , Anup Pramanik 4 , Rakesh Kundu 2 , Debabrata Mandal 5 , Naznin Ara Begum 1
Affiliation  

4′-N,N-Dimethylamino-3-hydroxyflavone (DMAHF), a synthetic fluorescent flavone analogue with potent antioxidant activity, was explored as a molecular rotor-like fluoroprobe for amyloid aggregations, a causative factor in Alzheimer’s disease, Parkinson’s disease, type-2 diabetes, etc. During its interactions with (human) insulin amyloid aggregation (IAA), its microenvironment was changed. This instigated a drastic change in its excited-state intramolecular proton transfer-based dual emission behavior, which was tracked to monitor its amyloid probing activity. Thus, the amyloid probing potential of DMAHF was originated from its interactions with IAA, which were studied by various spectroscopic techniques and molecular docking and quantum-mechanical calculations. Morphological changes of the IAA in the presence of DMAHF were studied by scanning electron microscopy. DMAHF also probed efficiently the islet amyloid polypeptide deposition in the pancreatic β-cells of diabetic mice. DMAHF showed significant sensitivity and specificity towards amyloid aggregation without having any complexity in its photophysical behavior. This indicates its potential as an ideal bio-friendly and cost-effective fluoroprobe for amyloid proteins.

中文翻译:

展现基于黄酮的荧光抗氧化剂对淀粉样蛋白错误折叠的作用:努力探索淀粉样蛋白聚集。

4'- ÑÑ-二甲基氨基-3-羟基黄酮(DMAHF)是一种具有有效抗氧化活性的合成荧光黄酮类似物,被研究为淀粉样蛋白聚集,阿尔茨海默氏病,帕金森氏病,2型糖尿病的致病因素的分子转子样氟探针。在与(人类)胰岛素淀粉样蛋白聚集体(IAA)相互作用期间,其微环境发生了变化。这激起了其基于激发态分子内质子转移的双重发射行为的剧烈变化,已对其进行跟踪以监测其淀粉样蛋白的探测活性。因此,DMAHF的淀粉样蛋白探测潜力源自其与IAA的相互作用,并通过各种光谱技术,分子对接和量子力学计算对其进行了研究。通过扫描电子显微镜研究了在存在DMAHF的情况下IAA的形态变化。DMAHF还有效地探测了糖尿病小鼠胰岛β细胞中胰岛淀粉样多肽的沉积。DMAHF对淀粉样蛋白聚集表现出显着的敏感性和特异性,而其光物理行为没有任何复杂性。这表明它作为淀粉样蛋白的理想生物友好型和高性价比氟探针的潜力。
更新日期:2020-12-10
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