Dataset Information

A Novel Aggregation-Induced Emission Fluorescent Probe for Detection of β-Amyloid Based on Pyridinyltriphenylamine and Quinoline-Malononitrile.

ABSTRACT: β-amyloid is an important pathological feature of Alzheimer's disease. Its abnormal production and aggregation in the patient's brain is an important basis for the early diagnosis and confirmation of Alzheimer's disease. In this study, a novel aggregation-induced emission fluorescent probe, PTPA-QM, was designed and synthesized based on pyridinyltriphenylamine and quinoline-malononitrile. These molecules exhibit a donor-donor-π-acceptor structure with a distorted intramolecular charge transfer feature. PTPA-QM displayed the advantages of good selectivity toward viscosity. The fluorescence intensity of PTPA-QM in 99% glycerol solution was 22-fold higher than that in pure DMSO. PTPA-QM has been confirmed to have excellent membrane permeability and low toxicity. More importantly, PTPA-QM exhibits a high affinity towards β-amyloid in brain sections of 5XFAD mice and classical inflammatory cognitive impairment mice. In conclusion, our work provides a promising tool for the detection of β-amyloid.

SUBMITTER: Fang Y

PROVIDER: S-EPMC10296659 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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A Novel Aggregation-Induced Emission Fluorescent Probe for Detection of β-Amyloid Based on Pyridinyltriphenylamine and Quinoline-Malononitrile.

Fang Yan Y Wang Qi Q Xiang Chenlong C Liu Guijin G Li Junjian J

Biosensors 20230602 6

β-amyloid is an important pathological feature of Alzheimer's disease. Its abnormal production and aggregation in the patient's brain is an important basis for the early diagnosis and confirmation of Alzheimer's disease. In this study, a novel aggregation-induced emission fluorescent probe, PTPA-QM, was designed and synthesized based on pyridinyltriphenylamine and quinoline-malononitrile. These molecules exhibit a donor-donor-π-acceptor structure with a distorted intramolecular charge transfer f ...[more]

PMID: 37366974

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Project description:Despite their unique advantages, the full potential of molecular probes for fluorescent monitoring of amyloid-β (Aβ) aggregates has not been fully exploited. This limited utility stems from the lack of knowledge about the hydrophobic interactions between the molecules of Aβ probes, as well as those between the probe and the Aβ aggregate. Herein, we report the first mechanistic study, which firmly establishes a structure-signaling relationship of fluorescent Aβ probes. We synthesized a series of five fluorescent Aβ probes based on an archetypal donor-acceptor-donor scaffold (denoted as SN1-SN5). The arylamino donor moieties were systematically varied to identify molecular factors that could influence the interactions between molecules of each probe and that could influence their fluorescence outcomes in conditions mimicking the biological milieu. Our probes displayed different responses to aggregates of Aβ, Aβ40 and Aβ42, two major isoforms found in Alzheimer's disease: SN2, having pyrrolidine donors, showed noticeable ratiometric fluorescence responses (Δν = 797 cm-1) to the Aβ40 and Aβ42 samples that contained oligomeric species, whereas SN4, having N-methylpiperazine donors, produced significant fluorescence turn-on signaling in response to Aβ aggregates, including oligomers, protofibrils, and fibrils (with turn-on ratios of 14 and 10 for Aβ42 and Aβ40, respectively). Mechanistic investigations were carried out by performing field-emission scanning electron microscopy, X-ray crystallography, UV-vis absorption spectroscopy, and steady-state and transient photoluminescence spectroscopy experiments. The studies revealed that the SN probes underwent preassembly prior to interacting with the Aβ species and that the preassembled structures depended profoundly on the subtle differences between the amino moieties of the different probes. Importantly, the studies demonstrated that the mode of fluorescence signaling (i.e., ratiometric response versus turn-on response) was primarily governed by stacking geometries within the probe preassemblies. Specifically, ratiometric fluorescence responses were observed for probes capable of forming J-assembly, whereas fluorescence turn-on responses were obtained for probes incapable of forming J-aggregates. This finding provides an important guideline to follow in future efforts at developing fluorescent probes for Aβ aggregation. We also conclude, on the basis of our study, that the rational design of such fluorescent probes should consider interactions between the probe molecules, as well as those between Aβ peptides and the probe molecule.

Dataset Information

A Novel Aggregation-Induced Emission Fluorescent Probe for Detection of β-Amyloid Based on Pyridinyltriphenylamine and Quinoline-Malononitrile.

Publications

A Novel Aggregation-Induced Emission Fluorescent Probe for Detection of β-Amyloid Based on Pyridinyltriphenylamine and Quinoline-Malononitrile.

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