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Beta-amyloid protein targeting fluorescent probe, preparation and application of beta-amyloid protein targeting fluorescent probe in Alzheimer's disease

A technology for Alzheimer's disease and amyloid protein, applied in the field of biomedicine, can solve the problems of difficult penetration and low sensitivity of iodinated probes, and achieve the effect of long emission wavelength, good response and enhanced fluorescence signal

Active Publication Date: 2021-06-08
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, PET has low sensitivity in imaging Aβ protein, MRI can only detect Aβ spots with a size larger than 50 μm, and the iodized probe in SPECT technology is difficult to penetrate the blood-brain barrier, and has radioactive radiation

Method used

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  • Beta-amyloid protein targeting fluorescent probe, preparation and application of beta-amyloid protein targeting fluorescent probe in Alzheimer's disease
  • Beta-amyloid protein targeting fluorescent probe, preparation and application of beta-amyloid protein targeting fluorescent probe in Alzheimer's disease
  • Beta-amyloid protein targeting fluorescent probe, preparation and application of beta-amyloid protein targeting fluorescent probe in Alzheimer's disease

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Experimental program
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Effect test

Embodiment 1

[0109] The preparation of embodiment 1 fluorescent probe compound (the synthetic route of fluorescent probe sees figure 1 , see the chemical structure figure 2 )

[0110] 1. The synthetic steps of compound 1;

[0111] First prepare the hydrochloric acid solution (HCl:H 2 O=1:1, v / v) 250ml, stir evenly, add 5.8g (42.6mmol) of N,N-dimethyl-1,4-p-phenylenediamine, after stirring evenly, add 7ml of crotonaldehyde, mix well Then, 30 ml of toluene was added to the reaction liquid, and the reaction was refluxed for 7 h under the protection of argon at 115° C. Thin-layer chromatography confirmed that the reaction was complete, the reaction was stopped, and the reaction was allowed to stand at room temperature. First remove the upper toluene solution, then adjust the pH to neutral with NaOH saturated solution under ice-water bath conditions, then add an equal volume of DCM to extract at least three times, and finally separate and purify by silica gel column chromatography (silica ...

Embodiment 2

[0321] (1) Preparation of Aβ aggregates;

[0322] The purchased Aβ1-42 aggregate protein (purchased from Qiangyao Biotechnology Co., Ltd.) was dissolved in 1% (v / v) ammonia water at a concentration of 100 μM, and continuously incubated at 37°C for one week to obtain Aβ1-42 aggregates.

[0323] (2) Determination of fluorescence spectrum

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Abstract

The invention discloses a beta-amyloid protein targeting fluorescent probe, preparation and application of the beta-amyloid protein targeting fluorescent probe in Alzheimer's disease. The structural formula of the fluorescent probe is as shown in formula I in the specification. The fluorescent probe disclosed by the invention is a compound taking 6-dimethylamino-1-methylquinoline as a parent structure, and the fluorescent probe has the advantages of long emission wavelength, large Stock shift, capability of specifically detecting beta amyloid protein, sensitivity to viscosity in tissue cells, and good response to the viscosity. After the fluorescent probe is combined with beta amyloid protein in the brain of a patient suffering from the Alzheimer's disease, a fluorescence signal is obviously enhanced, and the fluorescent probe can be used for detecting the beta amyloid protein and early diagnosing the Alzheimer's disease and has important guiding significance on development of diagnosis and treatment probes of the Alzheimer's disease.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a fluorescent probe targeting beta amyloid protein, its preparation and its application in Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is an irreversible neurodegenerative disease caused by multiple pathogenic factors. The clinical symptoms are mainly degenerative memory loss, cognitive and learning ability weakening, etc. The cause of Alzheimer's disease has not yet been fully understood. Through a large number of pathological studies, there are mainly three classic hypotheses for the pathogenic mechanism of Alzheimer's disease: Aβ protein deposition hypothesis, Tau protein hyperphosphorylation hypothesis and cholinergic neuron degeneration hypothesis. Among them, the hypothesis of Aβ protein deposition is extremely feasible. Among the pathological features, the main manifestation is the deposition of β-amyloid protein in the cerebral cor...

Claims

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Application Information

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IPC IPC(8): C07D215/38C07D409/06C07D401/06C07D405/06C09K11/06A61K49/00G01N21/64
CPCC07D215/38C07D409/06C07D401/06C07D405/06C09K11/06A61K49/0021G01N21/6428C09K2211/1029C09K2211/1088C09K2211/1092C09K2211/1007G01N2021/6439
Inventor 颜金武刘金胜张雷李晶
Owner SOUTH CHINA UNIV OF TECH