'Turn-On' Quinoline-Based Fluorescent Probe for Selective Imaging of Tau Aggregates in Alzheimer’s Disease: Rational Design, Synthesis, and Molecular Docking
| Autor: | Mengchao Cui, Seung Jae Hyeon, Ahmed A. Elbatrawy, Yun Kyung Kim, Hoon Ryu, Seung Hyeo Choi, Ghilsoo Nam, Sungsu Lim, Nan Yue, Essam Eldin A. Osman |
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| Rok vydání: | 2021 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
Tau protein tau Proteins Bioengineering 02 engineering and technology Fibril 01 natural sciences Turn (biochemistry) chemistry.chemical_compound Alzheimer Disease mental disorders Humans Instrumentation Fluorescent Dyes Fluid Flow and Transfer Processes Amyloid beta-Peptides biology Chemistry Process Chemistry and Technology 010401 analytical chemistry Quinoline Rational design Colocalization 021001 nanoscience & nanotechnology Fluorescence 0104 chemical sciences Molecular Docking Simulation Quinolines Biophysics biology.protein 0210 nano-technology |
| Zdroj: | ACS Sensors. 6:2281-2289 |
| ISSN: | 2379-3694 |
| DOI: | 10.1021/acssensors.1c00338 |
| Popis: | Tau aggregation is believed to have a strong association with the level of cognitive deficits in Alzheimer's disease (AD). Thus, optical brain imaging of tau aggregates has recently gained substantial attention as a promising tool for the early diagnosis of AD. However, selective imaging of tau aggregates is a major challenge due to sharing similar β-sheet structures with homologous Aβ fibrils. Herein, four quinoline-based fluorescent probes (Q-tau) were judiciously designed using the donor-acceptor architecture for selective imaging of tau aggregates. In particular, probe Q-tau 4 exhibited a strong intramolecular charge transfer and favorable photophysical profile, such as a large Stokes' shift and fluorescence emission wavelength of 630 nm in the presence of tau aggregates. The probe also displayed a "turn-on" fluorescence behavior toward tau fibrils with a 3.5-fold selectivity versus Aβ fibrils. In addition, Q-tau 4 exhibited nanomolar binding affinity to tau aggregates (Kd = 16.6 nM), which was 1.4 times higher than that for Aβ fibrils. The mechanism of "turn-on" fluorescence was proposed to be an environment-sensitive molecular rotor-like response. Moreover, ex vivo labeling of human AD brain sections demonstrated favorable colocalization of Q-tau 4 and the phosphorylated tau antibody, while comparable limited staining was observed with Aβ fibrils. Molecular docking was conducted to obtain insights into the tau-binding mode of the probe. Collectively, Q-tau 4 has successfully been used as a tau-specific fluorescent imaging agent with lower background interference. |
| Databáze: | OpenAIRE |
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