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Immunogenic peptide fragment of metalloproteinase ADAMTS-7 and application of immunogenic peptide fragment in resisting atherosclerosis and related diseases

An atherosclerosis and arterial technology, applied in the fields of biotechnology and medicine, can solve the problem of no effective short peptide vaccine reports, etc., achieve prevention or treatment of atherosclerosis and/or vascular restenosis, inhibit intimal neogenesis, Simple to use effects

Active Publication Date: 2021-03-26
北京经纬康泰生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Currently, no effective short peptide vaccines related to ADAMTS-7 have been reported

Method used

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  • Immunogenic peptide fragment of metalloproteinase ADAMTS-7 and application of immunogenic peptide fragment in resisting atherosclerosis and related diseases
  • Immunogenic peptide fragment of metalloproteinase ADAMTS-7 and application of immunogenic peptide fragment in resisting atherosclerosis and related diseases
  • Immunogenic peptide fragment of metalloproteinase ADAMTS-7 and application of immunogenic peptide fragment in resisting atherosclerosis and related diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Embodiment 1, the preparation of ADAMTS-7 vaccine and the detection of titer

[0055] 1. Screening of immunogenic peptides of metalloprotease ADAMTS-7

[0056] ADAMTS7 mainly promotes VSMC migration and angiogenesis intima formation by binding and degrading COMP. The present invention selects catalytic domain and 4TSP-1 like domain as target regions for screening short peptides. Enter the amino acid sequences of the catalytic domain and the 4 TSP-1like domain into the dialog box of IEDB B Cell EpitopePrediction respectively, and according to the predicted score, select 8, 9, 10, 11, and 12 amino acids in units of 8, 9, 10, 11, and 12 amino acids in the higher score For short peptides with a high overall score, input the amino acid sequences of the above two regions into the IEDB dialog box at the same time, select the existing Crystal Structure Of Adamts4 With InhibitorBound with the highest similarity to ADAMTS7 as the model for epitope prediction, and combine the two ...

Embodiment 2

[0067] Example 2, Vaccine DP-9 and Vaccine CD-9 Inhibit Neointimal Formation Caused by Ligation Model

[0068] 1. Establishment of the total ligation model of the left neck of mice after immunization

[0069] The experimental mice were male 6-week-old C57BL / 6 mice (purchased from the Department of Animals, Peking University Health Science Center), a total of 40 mice, weighing 21-23g, were randomly divided into 5 groups, 8 mice in each group, respectively experimental group 1, experimental Group 2, experimental group 3, experimental group 4 and control group.

[0070] The four kinds of dry powders of conjugates (KLH-CP9, KLH-DP9, KLH-CD9, KLH-CD8) obtained in step 2 of Example 1 were dissolved in sterile saline respectively, and the four concentrations were all 1 mg / mL the conjugate solution. The 4 kinds of conjugate solutions were mixed with aluminum hydroxide adjuvant (purchased from HEART, product number BF040) at a volume ratio of 10:1 to obtain 4 kinds of vaccines, namel...

Embodiment 3

[0073] Example 3, Vaccine DP-9 and Vaccine CD-9 Inhibit the Neointimal Formation Caused by the Guide Wire Strain Injury Model

[0074]1. Establishment of mouse wire strain injury model after immunization

[0075] The experimental mice were male 6-week-old C57BL / 6 mice (purchased from the Animal Department of Peking University Health Science Center), a total of 30 mice, weighing 21-23g, were randomly divided into 5 groups, 6 mice in each group, respectively experimental group 1, experimental Group 2, experimental group 3, experimental group 4 and control group.

[0076] The four kinds of dry powders of conjugates (KLH-CP9, KLH-DP9, KLH-CD9, KLH-CD8) obtained in step 2 of Example 1 were dissolved in sterile saline respectively, and the four concentrations were all 1 mg / mL the conjugate solution. The 4 kinds of conjugate solutions were mixed with aluminum hydroxide adjuvant (purchased from HEART, product number BF040) at a volume ratio of 10:1 to obtain 4 kinds of vaccines, nam...

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Abstract

The invention discloses an immunogenic peptide fragment of metalloproteinase ADAMTS-7 as well as a product and application of the immunogenic peptide fragment. The invention discloses an oligopeptidewhich comprises any one of the following: an oligopeptide with an amino acid sequence shown as a sequence 1 in a sequence table; an oligopeptide with an amino acid sequence shown as a sequence 2 in asequence table; an oligopeptide with an amino acid sequence shown as a sequence 3 in a sequence table; and an oligopeptide with an amino acid sequence shown as a sequence 4 in a sequence table. The invention further discloses a conjugate containing the oligopeptide, a vaccine containing the conjugate and application of the conjugate and the vaccine. The vaccine containing the oligopeptide can remarkably inhibit intima neogenesis of vascular restenosis mouse models and atherosclerosis of high-fat fed mice, and can be used for preventing or treating atherosclerosis and / or vascular restenosis.

Description

technical field [0001] The invention relates to the fields of biotechnology and medicine, in particular to the immunogenic peptide of metalloproteinase ADAMTS-7 and its application in anti-atherosclerosis and related diseases. Background technique [0002] Because of its high incidence and high mortality rate, coronary heart disease seriously endangers human health, so it is called "the first killer of human beings". The main cause of coronary heart disease is coronary atherosclerosis. The pathological process is that the abnormal accumulation of lipids in the blood vessel wall leads to the damage of endothelial cells in the blood vessel wall, the proliferation and migration of vascular smooth muscle cells, and the infiltration of inflammatory cells. Prominent plaque, the formation of plaque leads to narrowing of the lumen and insufficient blood supply. [0003] The treatment of coronary heart disease mainly includes statin lipid-lowering drug therapy and percutaneous coron...

Claims

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Application Information

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IPC IPC(8): C12N9/64C07K17/02A61K39/00A61P9/10
CPCC12N9/6491C07K17/02A61K39/0005A61P9/10A61K2039/6075A61K2039/6081A61P9/00C12Y304/24082C12N9/6489C07K16/40C07K2317/34A01K2207/30A01K2227/105A01K2267/0375A61K38/00A61K2039/55505C07K7/08C12N9/64A61K2039/6037
Inventor 孔炜付毅郑金刚马子涵廖玉华陈霄毛晨峰
Owner 北京经纬康泰生物科技有限公司
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