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B cell epitope for xanthine oxidase and antigen peptide containing epitope and applications thereof

A technology of xanthine oxidase and B cells, which is applied in the field of pharmaceutical preparations containing the novel peptide and its derivatives or analogs, can solve the problems of no reports of xanthine oxidase antibody inhibitors, and achieve important social and economic benefits , single ingredient, broad application prospects

Inactive Publication Date: 2017-01-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Research on xanthine oxidase antibody inhibitors based on xanthine oxidase B cell epitopes has no reports at home and abroad

Method used

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  • B cell epitope for xanthine oxidase and antigen peptide containing epitope and applications thereof
  • B cell epitope for xanthine oxidase and antigen peptide containing epitope and applications thereof
  • B cell epitope for xanthine oxidase and antigen peptide containing epitope and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Determination of the B-cell antigenic epitope of xanthine oxidase and the antigenic peptide of the B-cell antigenic epitope of said xanthine oxidase

[0025] Using B cell antigen epitope analysis software and online analysis tools, based on a single parameter, combined with secondary structure prediction and spatial structure characteristics, the dominant B cell antigen epitope RLEPYKKKNPS of xanthine oxidase was selected from hundreds of epitopes , see SEQ ID NO.1,

[0026] A linear B epitope of islet cell-specific antigen-insulin-related protein (IA-2) near the membrane region JM2 is selected, and its amino acid sequence is: FEYQD, and FEYQD and the B-cell epitope of xanthine oxidase are connected by Gly And inserted into the N-terminal of the Th2 helper cell epitope P2 peptide IPALDSLTPANED of P277 to form a new type of antigenic peptide named O-IA(5)-P2, the amino acid sequence is shown in SEQ ID No.4. And the antigenic peptides obtained by the transform...

Embodiment 2

[0028] Example 2: Identification of all the above-mentioned antigenic peptides and antigenic peptides obtained after modification

[0029] The experimental methods in the examples are conventional methods unless otherwise specified. All kits used were carried out in accordance with the conditions recommended by the manufacturer of the product.

[0030] 1. Establishment of diabetic model mice

[0031]A mouse model of diabetes mellitus (DM) was induced by multiple intraperitoneal injections of streptozotocin (STZ) in small doses. 4-week-old male C57BL / 6J mice (purchased from the Comparative Medicine Center of Yangzhou University, license number: SCXR (Su) 2014-0004) were prepared with 0.1M pH4.4 citrate buffer with a STZ concentration of 7.5mg / ml, Inject 50 mg / kg intraperitoneally, once a day, for 5 consecutive injections, measure the blood glucose level on the 7th and 14th days after modeling, and take the fasting blood glucose ≥ 11.1mmol / L for two consecutive times as the mo...

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Abstract

The invention discloses B cell epitope for xanthine oxidase and an antigen peptide containing the epitope. The antigen peptide is prepared by the following steps: B cell epitope for xanthine oxidase is connected to a linear B cell epitope FEYQD which is at a membrane-proximal region of insulinoma-associated protein-2 by a flexible peptide in a series connection, and a terminal is connected to a N terminal of Th2 auxiliary epitope P2 of P277 by a flexible peptide in a series connection. Serum which is obtained by immunization of mice with the antigen peptide is detected by Western blot, results show that an antibody which is specifically combined with xanthine oxidase is generated, and the antigen peptide is used for detecting xanthine oxidase; serum of the mice which are immunized by the antigen peptide can be used for inhibiting exogenous activity of xanthine oxidase, the difference between the inhibition rate of xanthine oxidase and the inhibition rate of allopurinol is not substantial (P>0.5), and the serum can be used for preparing xanthine oxidase inhibitor; the antigen peptide is used for treating gout, hepatopathy, nephrosis, atherosclerotic, diabetes, senile dementia, eye diseases, cardiovascular diseases, and other diseases due to xanthine oxidase abnormity, uric acid abnormity and oxidative stress disorder with important theoretical values and wide application prospects.

Description

technical field [0001] The present invention relates to the related fields of pharmacy and medicine, in particular to B epitopes predicted by xanthine oxidase, antigenic peptides containing the epitopes, and serum after immunizing animals with coupling proteins or fusion proteins to inhibit xanthine oxidase activity in vitro and Effects in therapeutic relevance, and pharmaceutical preparations containing the novel peptides and their derivatives or analogues. Background technique [0002] In recent years, with the improvement of people's living standards and dietary structure, the prevalence of gout at home and abroad has shown an upward trend, and has a tendency to become younger. According to the report of the National Health and Nutrition Survey in the United States, in terms of the incidence of gout, Males are at higher risk than females, with a male-to-female prevalence ratio between 7:1 and 9:1. The sex ratio tends to be flat with increasing age. The clinical symptoms...

Claims

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Application Information

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IPC IPC(8): C12N9/02C07K19/00C07K16/40G01N33/573A61K39/00A61P19/06A61P1/16A61P13/12A61P9/10A61P3/10A61P25/28A61P27/02A61P9/00
CPCC12N9/0093A61K39/00C07K14/4748C07K16/40C07K2319/00C12Y117/03002G01N33/573G01N2333/9029
Inventor 李泰明孟凯特马艳洁顾小骞焦琳方魏晓敏王岐信张婷婷
Owner CHINA PHARM UNIV
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