Anti-inflammatory antibacterial polypeptide capable of blocking combination of LPS and MD2

A technology of antibacterial polypeptide and lipopolysaccharide, applied in the field of medicine, can solve the problems of weak affinity and inability to impart TLR4 reactivity, etc.

Inactive Publication Date: 2010-08-18
INST OF FIELD OPERATION SURGERY NO 3 MILITARY MEDICL UNIV PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Data confirm that the affinity between CD14 and TLR4 / MD2 is weak, while the affinity between TLR4 / MD2 is strong, and the binding of MD2 (myeloid differential protein 2, myeloid differentiation protein 2) to TLR4 (toll like receptor 4, Toll-like receptor 4) Occurs before binding to LPS, and MD2, which has lost its LPS-binding function, cannot confer TLR4's responsiveness to LPS even if it binds to the extracellular region of TLR4

Method used

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  • Anti-inflammatory antibacterial polypeptide capable of blocking combination of LPS and MD2
  • Anti-inflammatory antibacterial polypeptide capable of blocking combination of LPS and MD2
  • Anti-inflammatory antibacterial polypeptide capable of blocking combination of LPS and MD2

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Experimental program
Comparison scheme
Effect test

specific Embodiment approach

[0028] The specific implementation method: (completed in six steps of experiment)

[0029] Experiment 1. Bioinformatics analysis of MD2 protein and selection of templates for screening antagonistic polypeptides.

[0030] Purpose of the experiment: To use bioinformatics technology to analyze the structural characteristics of MD2 protein, analyze parameters such as hydrophilicity, accessibility, flexibility, etc., and find the key amino acid sequence for the interaction between MD2 and the bacterial toxin LPS. And use this sequence as a template to lay the foundation for subsequent screening of its corresponding antagonistic polypeptides.

[0031] experimental method

[0032]1. Single-parameter prediction: Hydrophilicity, Antigenicity, Accessibility and Flexibility of the main chain of MD2.

[0033] 2. Secondary structure prediction and other information analysis: completed on PHD and SOPMA servers.

[0034] 3. Determination of cell epitopes: Summarize the single-parameter pr...

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Abstract

The invention provides anti-inflammatory antibacterial polypeptide capable of blocking combination of LPS and MD2. The amino acid sequence of the polypeptide is Ile Gly Lys Phe Leu Tyr Arg. The polypeptide can effectively lower septic inflammation damages induced by bacterial endotoxin LPS, obviously improve a survival rate of a mouse infected with endotoxin and keep the immune defense function of the organism while specifically inhibiting overstimulation of the LPS on inflammatory cells. The anti-inflammatory antibacterial polypeptide can be used for preparing medicaments for treating infections caused by gram-negative bacteria and inflammatory diseases induced by TLR4.

Description

technical field [0001] The invention belongs to the field of medicine, and mainly relates to an anti-inflammatory and antibacterial polypeptide capable of blocking the combination of LPS and MD2 and its pharmaceutical application, which is used to treat infection caused by Gram-negative bacteria and related excessive inflammation caused by it. damage diseases. Background technique: [0002] Sepsis caused by bacterial infection, especially Gram-negative bacterial infection, has become the main cause of death in clinical patients, especially surgical ICU patients. Data show that the proportion of sepsis in inpatients is 1 / 3, in ICU patients > 50%, and in surgical ICU is more than 80%. Unfortunately, despite the emergence of high-efficiency and broad-spectrum antibiotics, sepsis is still an important cause of death in clinical ICU patients. The main reason is a series of inflammatory damage caused by excessive stimulation of bacterial toxins on the body. Although the appli...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P31/04A61P29/00
Inventor 李磊闫红胡承香顾长国吴晓华
Owner INST OF FIELD OPERATION SURGERY NO 3 MILITARY MEDICL UNIV PLA
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