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A kind of hyperbranched polymer polypeptide and its preparation method and application

A technology of hyperbranched polymers and polymerized polypeptides, applied in the field of biochemistry, can solve the problems of ineffective stimulation of antigen presentation, short half-life of soluble peptides, and anaphylactic shock, so as to improve the severity of the disease, enhance immunogenicity, and recover Effects on walking ability

Active Publication Date: 2021-05-28
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reasons may include the short half-life of soluble peptides, which cannot effectively stimulate antigen presentation and induce immune tolerance; soluble peptides may cause anaphylactic shock and other potential safety issues through intravenous administration in some animal models

Method used

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  • A kind of hyperbranched polymer polypeptide and its preparation method and application
  • A kind of hyperbranched polymer polypeptide and its preparation method and application
  • A kind of hyperbranched polymer polypeptide and its preparation method and application

Examples

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Embodiment 1

[0023] The synthetic method of embodiment 1, hyperbranched polymer

[0024] The synthetic method of hyperbranched polymer, synthetic route such as figure 1 shown, including the following steps:

[0025] (1) Synthesis of S-Dodecyl-S'-(α,α'-dimethyl-α”-acetic acid)trithiocarbonate (DMATC): For its synthesis method, please refer to the use of new carbonate carboxyl-terminated as three efficient RAFT agent synthesis functions Sexual polymers (Macromolecules, 2002, 35(18), pp 6754–6756).

[0026] (2) Synthesis of DMATC-acrylate: DMATC chain transfer agent and acrylate cross-linked by the esterification of DMATC catalyzed by DMAP / EDC and hydroxyethyl acrylate, the specific method is as follows: in a 25ml round bottom flask, add 1.46g DMATC ( dodecyl trithiocarbonate), 1.15g EDC hydrochloride (C 8 h 17 N 3 HCl; 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride), 0.073g DMAP (4-dimethylaminopyridine), pre-dried in vacuum in the flask at room temperature (18-25°C) Overni...

Embodiment 2

[0031] Embodiment 2, hyperbranched polytrithiocarbonate modification

[0032] The obtained hyperbranched polytrithiocarbonate is further decomposed into polythiol by butylamine ammonolysis reaction under the protection of nitrogen. In order to prevent hyperbranched polythiols from cross-linking through thiol oxidation, thiols were converted into thioethers by gradually adding thiolene under nitrogen protection. The specific method was as follows: 0.6 g of hyperbranched polytrithiocarbonate was dissolved in 1.5 ml DCM (dichloromethane), then add 0.5ml butylamine (~20 times), and protect with nitrogen. After 30 min, the yellow solution faded to colorless or pale yellow, then nitrogen was bubbled into the solution to remove most of the DCM and butylamine. Nitrogen degassed hexane (-10 mL) was transferred to the solution to precipitate the product. After 15 minutes, a colorless or pale yellow product was adhering to the bottom of the bottle, and most of the solvent was removed t...

Embodiment 3

[0033] Example 3, preparation of hyperbranched polythioether acrylate crosslinked polypeptide

[0034] Both MOG and OVA polypeptide N-terminals have cysteine, 80mg hyperbranched polymer, 2mg peptide (OVA), 0.2mg butylamine mixed with 5ml water and stirred overnight, then put the solution into a dialysis bag (molecular weight cut-off: 3500Da) Dialyzed in deionized water for 2 days, and finally, the product was freeze-dried and purified to obtain hyperbranched polymeric polypeptide 3 (Hyper-branch polymer conjugated MOG-1, HB-OVA-1) and hyperbranched polymeric polypeptide 4 (Hyper-branch polymer conjugated MOG-1) -2, HB-OVA-2).

[0035] According to the same method, the difference is that the MOG polypeptide was used to obtain hyperbranched polymeric polypeptide 1 (Hyper-branchpolymer conjugated MOG-1, HB-MOG-1) and hyperbranched polymeric polypeptide 2 (Hyper-branchpolymer conjugated MOG-2, HB-MOG-1) respectively. MOG-2).

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Abstract

The invention relates to a hyperbranched polymeric polypeptide and its preparation method and application. The hyperbranched polymeric polypeptide is decomposed into polythiol by butylamine aminolysis of hyperbranched polymer 2 under the protection of nitrogen gas, and then the thiol is gradually added under the protection of nitrogen gas. Polymerized with polypeptide after converting thiol into thioether, the amino acid sequence of the polypeptide is shown in SEQ ID NO.1. The hyperbranched polymer polypeptide can stimulate the activation of antigen-presenting cells, and develop therapeutic treatment after cross-linking with the polypeptide Drugs for multiple sclerosis.

Description

technical field [0001] The invention belongs to the field of biochemistry, relates to a hyperbranched polymer polypeptide, and also relates to a preparation method and application of the hyperbranched polymer polypeptide. Background technique [0002] Autoimmune diseases such as multiple sclerosis are diseases caused by excessive activation of self-reactive T cells to attack self-tissues. We believe that antigen-specific treatment means targeting the elimination of self-reactive T cells in the immune system by inducing immune tolerance Therapeutic approach would be a very good strategy. The use of soluble self-epitope-specific peptides to induce immune tolerance for the treatment of autoimmune diseases has shown certain therapeutic effects in animal models, but many clinical trials have failed. The reasons may include the short half-life of soluble peptides, which cannot effectively stimulate antigen presentation and induce immune tolerance; soluble peptides may cause anaph...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K17/08A61K39/385A61P25/00A61P37/02
CPCA61K39/385A61K2039/6093C07K17/08
Inventor 李健刘雨青邢孟秋吴玉章
Owner ARMY MEDICAL UNIV
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