Elbatrawy, Ahmed A. Hyeon, Seung Jae Yue, Nan Osman, Essam Eldin A. Choi, Seung Hyeo Lim, Sungsu Kim, Yun Kyung Ryu, Hoon Cui, Mengchao Nam, Ghilsoo 2024-01-19T14:32:33Z 2024-01-19T14:32:33Z 2021-10-21 2021-06 https://pubs.kist.re.kr/handle/201004/116924 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 beta-sheet structures with homologous A beta fibrils. Herein, four quinoline-based fluorescent probes (Qtau) were judiciously designed using the donor-acceptor architecture for selective imaging of tau aggregates. In particular, probe Qtau 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 A beta fibrils. In addition, Qtau 4 exhibited nanomolar binding affinity to tau aggregates (K-d = 16.6 nM), which was 1.4 times higher than that for A beta 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 Qtau 4 and the phosphorylated tau antibody, while comparable limited staining was observed with A beta fibrils. Molecular docking was conducted to obtain insights into the tau-binding mode of the probe. Collectively, Qtau 4 has successfully been used as a tau-specific fluorescent imaging agent with lower background interference. English AMER CHEMICAL SOC "Turn-On" Quinoline-Based Fluorescent Probe for Selective Imaging of Tau Aggregates in Alzheimer's Disease: Rational Design, Synthesis, and Molecular Docking Article 10.1021/acssensors.1c00338 1 ACS Sensors, v.6, no.6, pp.2281 - 2289 ACS Sensors 6 6 2281 2289 N scie scopus 000668374500026 2-s2.0-85108991745 Chemistry, Multidisciplinary Chemistry, Analytical Nanoscience & Nanotechnology Chemistry Science & Technology - Other Topics Article PATHOLOGY PROGRESS PROTEIN LIGHT MODEL fluorescence imaging tau protein A beta fibrils Alzheimer&apos s disease molecular rotation