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Interleukin-17 receptor antagonist and application thereof in preparing anti-myocardial fibrosis medicine

A receptor blocker, interleukin technology, applied in the field of biomedicine, can solve the problems of large systemic side effects, unstable C-terminal of peptides, and limited drug research and development, achieving strong specificity and inhibiting receptor oligomerization. , the effect of high blocking efficiency

Active Publication Date: 2012-06-27
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the weak binding ability of anti-IL-17R antibody to IL-17, combined with its wide range of effects and large systemic side effects, it cannot be used in clinical practice, which limits its drug development as an IL-17 signaling antagonist
Some foreign studies have produced peptides that bind to IL-17R to block IL-17 signaling. The disadvantage is that the C-terminus of such peptides is unstable, which is not conducive to the maintenance of the molecular conformation of the peptides, resulting in biological instability.

Method used

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  • Interleukin-17 receptor antagonist and application thereof in preparing anti-myocardial fibrosis medicine
  • Interleukin-17 receptor antagonist and application thereof in preparing anti-myocardial fibrosis medicine
  • Interleukin-17 receptor antagonist and application thereof in preparing anti-myocardial fibrosis medicine

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Experimental program
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Effect test

Embodiment 1I

[0049] Embodiment 1 IL-17RA PLAD-IgG lentiviral vector construction

[0050] The construction and packaging of lentiviral vectors were assisted by Shanghai Yingweixin Biotechnology Co., Ltd.

[0051] 1. Experimental reagents and consumables

[0052] 1) Carrier: pLenO-DCE, the carrier map is as follows Figure 4 shown

[0053] 2) T4DNA ligase: NEB

[0054] 3) Restriction enzyme: NEB

[0055] 4) Gel recovery kit: Axygen

[0056] 5) PCR (enzymatic digestion) product purification kit: Axygen

[0057] 6) Thermosensitive phosphatase: NEB

[0058] 7) RNA extraction kit: Axygen

[0059] 8) MMLV First Strand cDNA Synthesis Kit: BBI

[0060] 9) DL2,000 DNA Marker: TaKaRa

[0061] 10) Electric constant temperature incubator: Shanghai Boxun Industrial Co., Ltd.

[0062] 11) Constant temperature shaker: Shanghai Sukun Industrial Co., Ltd.

[0063] 12) Electric constant temperature water bath: Shanghai Kanglu Experimental Instrument Co., Ltd.

[0064] 13) Electrophoresis instrum...

Embodiment 2I

[0150] Example 2 The effect of IL-17RA PLAD-Ig in anti-myocardial fibrosis

[0151] 1. Establishment of myosin-induced myocarditis model in rats

[0152] Materials: 6-week-old male Lewis rats were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.; purified porcine cardiac myosin was purchased from sigma company.

[0153] Method: 0.01M PBS and complete Freund's adjuvant added with 10 mg / ml Mycobacterium tuberculosis H37RA (Mycobacterium tuberculosis H37RA) were mixed according to the volume ratio of 1:1, and the mixed solution dissolved the purified porcine cardiac myosin ( Porcine cardiac myosin was purchased from Sigma-Aldrich, St Louis, MO, USA) to obtain immune emulsion for immunization of rats. Each rat was injected with 0.2 ml of the above-prepared emulsion from the footpad on day 0 and day 7 by a single subcutaneous injection. The rats after immunization were divided into two groups: IL-17RA PLAD-Ig group (n=13), on the 7th day, the ultrason...

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Abstract

The invention discloses interleukin-17 (IL-17) receptor antagonist which is characterized in that: the antagonist is peptide; the amino acid sequence of the peptide comprises a sequence with the number being SEQ ID No. 1 and the sequence with the number being SEQ ID No. 2 which are connected through a flexible connecting sequence; and the connecting order is sequentially the SEQ ID No. 1 sequence, the connecting sequence and the SEQ ID No. 2 sequence from a nitrogen end to a carbon end. According to the invention, IL-17RA PLAD and IgG Fc sections with the specificity existing in the IL-17 receptor form soluble fusion protein, are connected by flexible connecting protein Linker, do not affect the secondary structure of the protein, and can be separated and purified targeting at Ig. Consequently, the IL-17RAPLAD is closed, and the oligosaccharide of the receptor is suppressed. The interleukin-17 (IL-17) receptor antagonist has the advantages of high specificity, high blocking efficiency and the like.

Description

technical field [0001] The invention relates to a receptor antagonist and its application in preparing medicine, in particular to an interleukin-17 (IL-17) receptor antagonist and its application in preparing anti-myocardial fibrosis medicine. It belongs to the field of biomedical technology. Background technique [0002] In the latest worldwide analysis of causes of death, cardiovascular disease ranks among the top three, seriously threatening human life and health. Heart failure (heart failure, referred to as heart failure), as the final stage of the development of various heart diseases, is becoming the most important cause of cardiovascular death in this century. Epidemiological data show that the number of heart failure patients worldwide has reached 22.5 million and is still increasing at a rate of 2 million per year. The 5-year survival rate is similar to that of malignant tumors, and it has become a major public health problem worldwide. [0003] The focus of previ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N15/62C12N15/63C12N1/15C12N1/19C12N1/21C12N5/10A61K38/17A61K47/48A61P29/00A61P9/00
Inventor 刘巍高成尹鹏志刘颖宋云艳
Owner HARBIN MEDICAL UNIVERSITY
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