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Peptoid inhibitor as well as preparation method and application thereof

A technology of peptide inhibitors and inhibitors, applied in the field of biomedicine, can solve the problems of complicated preparation steps and difficult industrial production, and achieve the effect of reducing toxic effects

Active Publication Date: 2016-07-13
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the preparation steps of the compound are too complicated to realize industrial production

Method used

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  • Peptoid inhibitor as well as preparation method and application thereof
  • Peptoid inhibitor as well as preparation method and application thereof
  • Peptoid inhibitor as well as preparation method and application thereof

Examples

Experimental program
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Effect test

experiment example 1

[0051] Preparation of Experimental Example 1 Peptide Inhibitor API1

[0052] The peptide inhibitor API1 of the present invention is synthesized by a solid-phase subunit synthesis method, the method comprising the following steps:

[0053] (1) Add 2M bromoacetic acid and 3.2M N,N'-diisopropylcarbodiimide (DIC) to Rink amide AM resin (substitution level 0.3mmol / g), react at 37°C for 30min, and the resin end Amino acylation;

[0054] (2) Add 2M primary amine and react at 37°C for 90 minutes, and replace the bromine atom by nucleophilic displacement reaction to complete the synthesis of a subunit;

[0055] (3) Steps (1) and (2) are repeated until the synthesis of the remaining subunits is completed;

[0056] (4) After the synthesis is completed, the side chain protecting group is removed, and API1 is cleaved from the resin with 95% trifluoroacetic acid, 2.5% ultrapure water, and 2.5% triisopropylsilane for future use.

[0057] The molecular formula of the prepared API1 is as fo...

experiment example 2

[0061] Experimental Example 2 Changes in the morphology of β-amyloid polypeptide Aβ1-42 aggregates by the peptide inhibitor API1

[0062] The β-amyloid polypeptide Aβ1-42 was dissolved in phosphate buffer and incubated with the peptoid inhibitor API1 for 48 hours at 37°C with constant temperature shaking, and the effect of API1 on the aggregation morphology of Aβ1-42 was observed by atomic force microscopy. The characterization of the influence of API1 on the aggregation morphology of Aβ1-42 comprises the following steps:

[0063] (1) Dissolving Aβ1-42 in phosphate buffer solution with pH 7.2 to make a 20 μM solution;

[0064] (2) API1 and Aβ1-42 were mixed equimolarly, dissolved in phosphate buffer solution of pH 7.2 to prepare a mixed buffer solution, the concentrations were respectively 200 μM and 20 μM, and co-incubated at 37° C. for 24 hours;

[0065] (3) Add the mixed solutions obtained in steps (1) and (2) dropwise onto flat substrates such as mica and silicon wafers, ...

experiment example 3

[0067] Experimental Example 3 Aggregation Inhibitory Effect of Peptide Inhibitor API1 on Aβ1-42 Polypeptide

[0068] The specific steps for detecting the aggregation inhibitory effect of the peptide inhibitor API1 of the present invention on the Aβ1-42 polypeptide using ThT fluorescence technology are as follows:

[0069] (1) Prepare 20 μM Aβ1-42 solution, Aβ1-42:API1=1:1, 1:5 and 1:10 mixed buffer;

[0070] (2) adding THT fluorescent dye to the solution configured in step (1);

[0071] (3) Test the mixed solutions obtained in step (2) respectively. Select a specific excitation wavelength and emission wavelength, and reflect the aggregation degree of Aβ1-42 in the solution by testing the fluorescence intensity at the emission wavelength.

[0072] The experimental condition is 37°C, and the test is performed every 15 minutes. The results are as follows: figure 2 As shown, API1:Aβ1-42=1:1, 1:5, and 1:10 respectively gradually strengthened the aggregation inhibitory effect on ...

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Abstract

The invention provides a peptoid inhibitor as well as a preparation method and application thereof, relates to the technical field of biomedicine and specifically relates to a peptoid, in particular to a polypeptide-aggregated peptoid inhibitor capable of inhibiting Abeta1-42. The peptoid inhibitor is prepared from Npip, Nmba, Nlys and Nleu subunits. The peptoid inhibitor API 1 is an inhibitor which is high in water solubility, low in cytotoxicity and high in associative property with beta-islet amyloid polypeptide, thereby providing a new selection for researching medicaments for treating Alzheimer's disease.

Description

technical field [0001] The invention relates to the field of biomedical technology, in particular to a peptoid, and in particular to a peptoid inhibitor for inhibiting Aβ1-42 polypeptide aggregation. Background technique [0002] Amyloid disease is a general term for more than 20 diseases caused by amyloid aggregation, including Alzheimer's disease (commonly known as senile dementia) (Alzheimer'disease, AD), Parkinson's disease (Parkinson'disease, PD) ), chorea (Huntington's disease, HD) and so on. The lesion sites of different amyloid diseases are different, mainly involving the nervous system, heart, liver, kidney, etc. Some protein monomers are non-toxic or very toxic, but they can aggregate into oligomers or fibrils with toxic effects and cause a series of diseases, such as β-amyloid (Aβ) can cause AD, α-synuclein can cause PD, prion protein (PrionproteinPrP) can cause at least ten kinds of encephalopathy in humans and animals including mad cow disease, and polypeptide...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/04A61K38/08A61P25/28A61P25/16A61P25/14A61P3/10
CPCA61K38/00C07K7/06
Inventor 朱凌赵子健覃茂昌杨延莲胡志远
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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