Dataset Information

Sensing Performance Investigations on Two-Photon Fluorescent Probes for Detecting ?-Amyloid in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is one of the most common forms of senile disease. In recent years, the incidence of AD has been increasing significantly with the acceleration of the aging process of the global population. However, current clinical drugs can only alleviate the symptoms of AD patients without healing the disease fundamentally. Therefore, it is of great significance to develop an effective small molecule diagnostic reagent for the early diagnosis of AD. In this paper, we employ an integrated approach, including molecular docking simulation and quantum mechanics/molecular mechanics calculation, to investigate the sensing performance of a series of donor-acceptor structural probes for the marker protein of AD (?-amyloid). Results show that the probes display evident fluorescence enhancement when bound to the ?-amyloid, suggesting the effect of the environment on the molecular properties. Especially, the two-photon absorption cross-section of the probes increase drastically in the ?-amyloid compared to that in vacuum, which results from the larger electron delocalization and dipole moment in the fibrillary-like environment. Thus, one can propose that the studied probes are capable of application in two-photon fluorescent imaging, particularly those containing naphthalene rings as the donor or with a longer spacer group. Our calculations elucidate the experimental measurements reasonably, and further establish possible structure-property relationships that can be used to design novel biocompatible two-photon fluorescent probes for the diagnosis of Alzheimer's.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7146205 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Sensing Performance Investigations on Two-Photon Fluorescent Probes for Detecting <i>β</i>-Amyloid in Alzheimer's Disease.

Zhang Yujin Y Luan Ni N Li Kan K Leng Jiancai J Hu Wei W

Sensors (Basel, Switzerland) 20200322 6

Alzheimer's disease (AD) is one of the most common forms of senile disease. In recent years, the incidence of AD has been increasing significantly with the acceleration of the aging process of the global population. However, current clinical drugs can only alleviate the symptoms of AD patients without healing the disease fundamentally. Therefore, it is of great significance to develop an effective small molecule diagnostic reagent for the early diagnosis of AD. In this paper, we employ an integr ...[more]

PMID: 32235776

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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

Sensing Performance Investigations on Two-Photon Fluorescent Probes for Detecting ?-Amyloid in Alzheimer's Disease.

Publications

Sensing Performance Investigations on Two-Photon Fluorescent Probes for Detecting <i>β</i>-Amyloid in Alzheimer's Disease.

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