Preparation method and application of polypeptide functionalized composite micelle for inhibiting aggregation of alpha-synuclein

A technology of synuclein and composite micelles, which is applied in the field of preparation of composite micelles, and can solve the problems of poor remote adsorption effect and non-specificity

Pending Publication Date: 2021-05-28
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

For example, composite shell nanomicelles that can have hydrophobic regions under physiological conditions have good biocompatibility, stable structure, an...

Method used

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  • Preparation method and application of polypeptide functionalized composite micelle for inhibiting aggregation of alpha-synuclein
  • Preparation method and application of polypeptide functionalized composite micelle for inhibiting aggregation of alpha-synuclein
  • Preparation method and application of polypeptide functionalized composite micelle for inhibiting aggregation of alpha-synuclein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: Preparation of a polypeptide-functionalized composite micelle that inhibits α-synuclein aggregation.

[0031] 1) Synthesis of βsyn36-PEG-b-PCL

[0032] Select βsyn36 (polypeptide sequence: GVLYVGSKTR) as the specific recognition peptide, dissolve 90mg of MAL-PEG-PCL and 20mg of polypeptide (C-GG-GVLYVGSKTR) in DMF treated by vacuum distillation, add 50ul of triethylamine, at room temperature The reaction was carried out under stirring for 24 hours. After the reaction was completed, the reaction solution was transferred to a dialysis bag for dialysis, and lyophilized to obtain βsyn36-PEG-PCL.

[0033] 2) Synthesis of PCL-b-PAE

[0034] Weigh 80 mg of hydroxyethyl acrylate (HMA) and 4 g of ε-CL, add them to an eggplant-shaped bottle, add 10 ml of toluene to dissolve, add 2 drops of stannous octoate as a catalyst, freeze in liquid nitrogen-fill with nitrogen-thaw for three times, and react in The reaction was carried out in an oil bath at 110°C for 12 hours, a...

Embodiment 2

[0038] Example 2: Preparation of a polypeptide-functionalized composite micelle that inhibits α-synuclein aggregation.

[0039] 1) Synthesis of βsyn36-PEG-b-PCL

[0040] Select βsyn36 (polypeptide sequence: GVLYVGSKTR) as the specific recognition peptide, dissolve 90mg of MAL-PEG-PCL and 20mg of polypeptide (C-GG-GVLYVGSKTR) in DMF treated by vacuum distillation, add 50ul of triethylamine, at room temperature The reaction was carried out under stirring for 24 hours. After the reaction was completed, the reaction solution was transferred to a dialysis bag for dialysis, and lyophilized to obtain βsyn36-PEG-PCL.

[0041] 2) Synthesis of PCL-b-PAE

[0042] Weigh 80 mg of hydroxyethyl acrylate (HMA) and 4 g of ε-CL, add them to an eggplant-shaped bottle, add 10 ml of toluene to dissolve, add 2 drops of stannous octoate as a catalyst, freeze in liquid nitrogen-fill with nitrogen-thaw for three times, and react in The reaction was carried out in an oil bath at 110°C for 12 hours, and...

Embodiment 3

[0046] Example 3: Preparation of a polypeptide-functionalized composite micelle that inhibits α-synuclein aggregation.

[0047] 1) Synthesis of βsyn36-PEG-b-PCL

[0048] Select βsyn36 (polypeptide sequence: GVLYVGSKTR) as the specific recognition peptide, dissolve 90mg of MAL-PEG-PCL and 20mg of polypeptide (C-GG-GVLYVGSKTR) in DMF treated by vacuum distillation, add 50ul of triethylamine, at room temperature The reaction was carried out under stirring for 24 hours. After the reaction was completed, the reaction solution was transferred to a dialysis bag for dialysis, and lyophilized to obtain βsyn36-PEG-PCL.

[0049] 2) Synthesis of PCL-b-PAE

[0050] Weigh 80 mg of hydroxyethyl acrylate (HMA) and 4 g of ε-CL, add them to an eggplant-shaped bottle, add 10 ml of toluene to dissolve, add 2 drops of stannous octoate as a catalyst, freeze in liquid nitrogen-fill with nitrogen-thaw for three times, and react in The reaction was carried out in an oil bath at 110°C for 12 hours, a...

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Abstract

The invention relates to a preparation method and application of a polypeptide functionalized composite micelle for inhibiting aggregation of alpha-synuclein. The polypeptide functionalized composite micelle is composed of two amphiphilic block copolymers, including a non-physiological environment responsive amphiphilic block copolymer with functionalized polypeptide at a hydrophilic end and an amphiphilic block copolymer with physiological environment responsiveness at a hydrophilic end, and the micelle forms a core-shell-crown structure under physiological conditions. The surface polypeptide specifically recognizes the alpha-synuclein, when the alpha-synuclein tends to gather, the surface polypeptide pulls the alpha-synuclein aggregate to be close to a shell hydrophobic region, so the hydrophobic region efficiently adsorbs the alpha-synuclein aggregate, and the hydrophobic region is divided into independent cells by a hydrophilic end without environmental responsiveness; and the aggregate is prevented from further gathering. The polypeptide functionalized composite micelle is simple in preparation process and good in biocompatibility, can efficiently inhibit alpha-synuclein aggregation, and has a wide application prospect in the aspect of early treatment of Parkinson's disease.

Description

technical field [0001] The invention belongs to the field of nano biomedical materials, and relates to a preparation method and application of a polypeptide-functionalized compound micelle that inhibits alpha-synuclein aggregation. Background technique [0002] Parkinson's disease (PD) is a neurodegenerative disease that mainly occurs in the elderly. Its clinical manifestations mainly include resting tremor, muscle rigidity, slow movement and postural balance disorder, and patients may be accompanied by depression, smell disturbance and sleep disturbance. Disorders and other symptoms seriously affect the lives of patients and their families. The main pathological features of PD are the damage of dopaminergic neurons in the substantia nigra of the midbrain and the appearance of Lewy bodies. Among them, α-synuclein is an important component of Lewy bodies. The current treatment strategies mostly target dopamine and treat with levodopa drugs, but these drugs cannot fundamenta...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/64A61P25/16B82Y5/00B82Y30/00B82Y40/00
CPCA61K47/64A61K47/6907B82Y5/00B82Y30/00B82Y40/00A61P25/16
Inventor 史林启武晓慧马飞贺刘阳马如江安英丽
Owner NANKAI UNIV
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