A High Affinity Red Fluorescence and Colorimetric Probe for Amyloid β Aggregates.
A High Affinity Red Fluorescence and Colorimetric Probe for Amyloid β Aggregates.
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DOI：
10.1038/srep23668
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发表时间：
2016-04-01
影响因子：
4.6
通讯作者：
Govindaraju T
中科院分区：
文献类型：
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作者：
Rajasekhar K;Narayanaswamy N;Murugan NA;Kuang G;Ågren H;Govindaraju T
阿尔茨海默病（AD）的一个主要挑战是其及时诊断。β淀粉样蛋白（Aβ）聚集体已被认为是诊断AD最可行的生物标志物。在这里，我们证明了基于半花菁的苯并噻唑香豆素（TC）作为一种潜在的探针，通过开启、增强（约30倍）的红色荧光（Emax = 654 nm）和特征比色（浅红色至紫色）光输出检测高毒性Aβ42聚集体。有趣的是，与其他异常蛋白质聚集体相比，TC对Aβ42原纤维表现出选择性。TC探针对Aβ42聚集体显示出纳摩尔结合亲和力（Ka = 1.72 × 107 M−1），并且由于其高结合亲和力，还取代了与Aβ42原纤维结合的ThT。TC吸收光谱中的Aβ42纤维特异性红移导致观察到的比色光输出，这归因于探针周围的微环境从类亲水性变化为类疏水性。TC与Aβ42纤维相互作用的结合位点、结合能和光学性质的变化已通过分子对接和时间依赖密度泛函理论研究得到进一步验证。
A major challenge in the Alzheimer’s disease (AD) is its timely diagnosis. Amyloid β (Aβ) aggregates have been proposed as the most viable biomarker for the diagnosis of AD. Here, we demonstrate hemicyanine-based benzothiazole-coumarin (TC) as a potential probe for the detection of highly toxic Aβ42 aggregates through switch-on, enhanced (~30 fold) red fluorescence (Emax = 654 nm) and characteristic colorimetric (light red to purple) optical outputs. Interestingly, TC exhibits selectivity towards Aβ42 fibrils compared to other abnormal protein aggregates. TC probe show nanomolar binding affinity (Ka = 1.72 × 107 M−1) towards Aβ42 aggregates and also displace ThT bound to Aβ42 fibrils due to its high binding affinity. The Aβ42 fibril-specific red-shift in the absorption spectra of TC responsible for the observed colorimetric optical output has been attributed to micro-environment change around the probe from hydrophilic-like to hydrophobic-like nature. The binding site, binding energy and changes in optical properties observed for TC upon interaction with Aβ42 fibrils have been further validated by molecular docking and time dependent density functional theory studies.