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Short peptide targeting ikkβ and its application in inflammatory diseases

An inflammatory response and short peptide technology, applied in the field of biomedicine, can solve problems such as tissue damage, and achieve the effects of weak side effects, easy tracking and observation, and easy processing and synthesis.

Active Publication Date: 2021-12-24
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The inflammatory response is a protective host response to infection and tissue damage; normally, the inflammatory response is beneficial for the host to clear infection; however, a dysregulated inflammatory response can lead to excessive or prolonged tissue damage, leading to acute or chronic inflammation disease development

Method used

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  • Short peptide targeting ikkβ and its application in inflammatory diseases
  • Short peptide targeting ikkβ and its application in inflammatory diseases
  • Short peptide targeting ikkβ and its application in inflammatory diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: Screening of IKIP Action Regions

[0051] The results of the study showed that the IκB kinase binding protein IKIP has a significant binding effect on IKKβ, which inhibits the combination of IKKβ and IKKγ, thereby inhibiting the formation of IKK complex, restricting the entry of p65 into the nucleus, and finally inhibiting the expression of inflammatory cytokines, thereby inhibiting inflammation. The function of the response; cell experiments and animal experiments have shown that the loss of IKIP will lead to a significant increase in inflammatory response. The applicant found that the function of IKIP is mainly dependent on its N-terminal structure, in which the binding protein IKIP of IKKβ competes with IKKγ through 99 amino acids at positions 1-99 of the N-terminus. IKKα / β inhibits the formation of the IKK complex, thereby hindering IKKα / β phosphorylation process and negatively regulate the activation of downstream NF-κB signaling pathway. Therefore, a ...

Embodiment 2

[0063] Example 2: Verifying the effect of short peptides on the expression of inflammatory cytokines

[0064] (1) Short peptides (5 μM) F0, F1, and F2 were added to mouse peritoneal macrophages in advance for pretreatment, and then stimulated by adding LPS, PGN, TNFα, and IL-1β 2 hours later, at different time points by RT- The mRNA levels of inflammatory cytokines TNF-α and IL-6 were detected by PCR.

[0065](2) Short peptides (5μM) F0, F1, and F2 were added to mouse peritoneal macrophages in advance for pretreatment, and then stimulated by adding LPS and PGN respectively after 2 hours. After 24 hours of culture, the inflammatory cytokine TNF-α was detected by ELISA , IL-6 secretion level.

[0066] (3) Short peptides (5μM) F0, F1, and F2 were added to mouse peritoneal macrophages in advance for pretreatment. After 2 hours, LPS, PGN, TNFα, IL-1β and other stimuli were added, and Western Blot was used at different time points. Detect the phosphorylation level of adapter prote...

Embodiment 3

[0070] Example 3: Verifying the effect of short peptides on the IKK complex

[0071] (1) 293T cells, overexpressing IKKβ-HA plasmid, adding short peptides F0, F1, F2 (5μM) 24 hours after transfection, adding IP Buffer 2 hours later to lyse the cells. Take 50 μL of cell lysate as Input, and add 50 μL of StreptavidinBeads to the remaining samples. After shaking for 4 hours in a silent mixer, wash the beads with 1000 g of IP Buffer for 4 minutes*4 times. The combination of short peptide and IKKβ was detected by Western Blot.

[0072] (2) 293T cells overexpressed IKKα-Myc, IKKβ-Myc, and IKKγ-Myc, and 24 hours after transfection, short peptide F1 (5 μM) was added. After continuing to culture for 2 hours, IP Buffer lysed the cells. Take 50 μL of cell lysate as Input, and add 50 μL of Streptavidin Beads to the remaining samples. After shaking for 4 hours in a silent mixer, wash the beads with 1000 g of IP Buffer for 4 min*4 times. Western Blot was used to detect the combination of...

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Abstract

The invention belongs to the field of biomedicine, in particular to a short peptide targeting IKKβ and its application in inflammatory diseases. In order to provide a more effective treatment for inhibiting inflammatory responses, the present application provides a short peptide targeting IKKβ, the short peptide includes the N-terminal amino acid 46-60 region derived from the IκB kinase binding protein IKIP, and the N-terminal of the short peptide is fused through Membrane peptides, with peptide tags. The short peptide can target IKKβ, inhibit the combination of IKKβ and IKKγ, thereby inhibiting the formation of IKK complex, reducing the expression of inflammatory cytokines TNF-α and IL-6, and inhibiting the inflammatory response. Animal models have shown that short peptides can effectively treat arthritis and inflammatory bowel disease. Compared with the full-length protein, the short peptide has a small molecular weight, is easy to synthesize, has weak immunogenicity, and has relatively weak side effects; it has better absorption with cell-penetrating peptides, and is easy to track and observe with peptide tags, which is a great tool for clinical treatment of inflammatory diseases for reference.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a short peptide targeting IKKβ or a pharmaceutical composition and / or auxiliary pharmaceutical composition for inhibiting inflammatory response or preventing / treating inflammatory response diseases or a short peptide targeting IKKβ Use of the peptide in the preparation of products for inhibiting inflammatory responses or preventing or treating inflammatory response diseases. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] The inflammatory response is a protective host response to infection and tissue damage; normally, the inflammatory response is beneficial for the host t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/17A61K47/64A61P29/00
CPCC07K14/47A61P29/00C07K2319/10A61K38/00
Inventor 高成江张磊柳翰森吴海峰赵学英郑义刘冰玉
Owner SHANDONG UNIV
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