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Immunogenic peptide fragments of [alpha]1D-adrenergic receptor for hypertension treatment and application thereof

An immunogenic and adrenaline-based technology, applied in the direction of hormone receptors, receptors/cell surface antigens/cell surface determinants, carrier-bound antigens/hapten components, etc., can solve the problem that there is no α1-AR and blockers on the market and other problems, to achieve the effect of strong specificity, strong antihypertensive effect, and protection of target organs

Active Publication Date: 2019-10-15
WUHAN HUAJIYUAN BIOTECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] So far, there is no blocker specifically targeting α1-AR on the market in the world, especially the blocker targeting α1D-AR

Method used

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  • Immunogenic peptide fragments of [alpha]1D-adrenergic receptor for hypertension treatment and application thereof
  • Immunogenic peptide fragments of [alpha]1D-adrenergic receptor for hypertension treatment and application thereof
  • Immunogenic peptide fragments of [alpha]1D-adrenergic receptor for hypertension treatment and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: Preparation of α1D-AR Immunogenic Peptides

[0037]According to the characteristics of amino acid hydrophilicity, spatial conformation, and B cell epitope, the immunogenic peptide CGITEEXGY of α1D-adrenergic receptor is designed, as shown in SEQ ID No.1, where X is V, A, L and any one of I;

[0038] At the same time, the present invention optimizes two immunogenic peptides, the amino acid sequences of which are respectively CGITEEVGY shown in SEQ ID No.2, named CY-9 and CGITEEAGY shown in SEQ ID No.3, named ADR-004;

[0039] The PSSM-8 peptide automatic synthesizer (SHIMADZU, Japan) was used to synthesize the above 2 peptides, and the purity of the 2 peptides was analyzed by high performance liquid chromatography. Reach more than 98%. The obtained 2 peptides were lyophilized, aliquoted, placed in cryopreservation tubes, and stored at -80°C for later use.

Embodiment 2

[0040] Example 2: Preparation of α1D-AR immunogenic vector vaccine

[0041] 1. Using the Qβ-2aa bacteriophage virus-like particle protein, prepare two vector vaccines: ADRQβ-CY-9 and ADRQβ-004. Concrete preparation process is as follows:

[0042] 1) Preparation of Qβ-2aa phage virus-like particle protein carrier: the English abbreviation of Qβ-2aa bacteriophage virus-like particle protein is: Qβ-2aa VLP, and Qβ-2aa VLP is used to represent Qβ-2aa bacteriophage virus-like particle protein hereinafter.

[0043] The preparation method of Qβ-2aa VLP is:

[0044] 1a) Obtaining a recombinant strain expressing Qβ-2aa VLP: the recombinant strain is Escherichia coli DH5α / pGEXQβ-A1, and this recombinant strain can induce the production of Qβ-2aa VLP protein. The preservation number of Escherichia coli DH5α / pGEXQβ-A1 is CCTCCNO: M209282. For the specific preparation process, please refer to the Chinese patent: A Qβ-2aa bacteriophage virus-like particle protein preparation method and it...

Embodiment 3

[0057] Example 3: Effect of α1D-AR Immunogenic Vector Vaccine on Blood Pressure Levels of Spontaneously Hypertensive Rats

[0058] The vector vaccines ADRQβ-CY-9 and ADRQβ-004 were regularly immunized in spontaneously hypertensive rats (SHR) to investigate whether the α1D-AR immunogenic vector vaccine could reduce the blood pressure of SHR. The specific test process is:

[0059] 1) 4-week-old male SHRs were selected for active immunization, and they were divided into 3 groups as follows:

[0060] The first group: blank control group (control): on the 6th, 20th and 34th days, PBS was injected subcutaneously at multiple points on the back respectively, the dose was 300 μl / rat, 10 rats in total;

[0061] The second group: ADRQβ-004 vaccine group (ADRQβ-004): On the 6th, 20th and 34th days, the carrier vaccine ADRQβ-004 was subcutaneously immunized at multiple points on the back respectively, with a dose of 300 μg / rat, a total of 8 rats;

[0062] The third group: ADRQβ-CY-9 vacc...

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Abstract

The invention discloses immunogenic peptide fragments of an [alpha]1D-adrenergic receptor for hypertension treatment and application thereof. The amino acid sequences of the immunogenic peptide fragments are CGITEEXGY as SEQ ID No.1, wherein X is a random amino acid. Immunogenic vector-based vaccines for the [alpha]1D-adrenergic receptor are prepared by coupling the immunogenic peptide fragments with a vector. The designed two immunogenic peptide fragments are successfully coupled to a Q[beta]-2aa Bacteriophage virus-like particle protein vector respectively to prepare the two vector-based vaccines. The vaccines can be used for preparing medicines treating hypertension.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to an immunogenic peptide segment of α1D-adrenoceptor for treating hypertension and its application. Background technique [0002] Hypertension is a worldwide problem that seriously endangers human health and is a major risk factor for cardiovascular and cerebrovascular diseases. At present, the prevalence and mortality of cardiovascular diseases in my country are still on the rise. It is estimated that there are about 270 million people with high blood pressure in the country. 2016). Although the treatment of hypertension has made great progress, the high incidence and very low control rate of hypertension still exist, so people are constantly looking for new means to improve this situation. [0003] The occurrence and development of hypertension involves complex pathophysiological mechanisms, among which the hyperactivity of the sympathetic nervous system is involved in the occurrenc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/72A61K39/00A61K39/385A61P9/12
CPCC07K14/72A61K39/0005A61K39/385A61P9/12A61K2039/6075
Inventor 廖玉华邱志华李畅廖梦阳
Owner WUHAN HUAJIYUAN BIOTECH DEV
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