Decoy Peptides Inhibit SEFIR Domain Binding for IL-17 Disease Treatment
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Solution Overview
Problem
Current treatments for inflammatory and autoimmune diseases, such as asthma and rheumatoid arthritis, often rely on NSAIDs and steroids that have severe side effects, and there is a need for more effective IL-17 blockers to manage IL-17-mediated signaling.
Innovation Solution
Development of cell-permeable decoy peptides that competitively inhibit the binding of the SEFIR domain of IL-17R to the SEFIR domain of Act1, specifically targeting the αC helix region, to disrupt IL-17-mediated signaling and inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If NSAIDs and steroids are used to treat inflammatory and autoimmune diseases, then inflammation is suppressed, but severe side effects occur
Solution Approach 1:
The patent uses decoy peptides as intermediary molecules that specifically bind to the SEFIR domain of Act1, preventing its interaction with IL-17R. This targeted intervention blocks IL-17-mediated signaling pathways responsible for inflammation without triggering the broad immunosuppression and severe side effects associated with conventional NSAID and steroid treatments.
Solution Approach 2:
The invention extracts and isolates the specific molecular interaction (SEFIR domain binding) that mediates IL-17 signaling. By designing decoy peptides that specifically target this extracted interaction interface, the treatment achieves precise anti-inflammatory effects while avoiding the non-specific toxicity of conventional broad-spectrum anti-inflammatory drugs.
2Object-affected harmful factors
If conventional anti-inflammatory treatments are used, then inflammation is reduced, but treatment effectiveness is limited by severe side effects
Solution Approach 1:
Decoy peptides serve as safe intermediary molecules that specifically intercept the pathological SEFIR-SEFIR interaction without disrupting normal physiological functions. This high-specificity mechanism provides reliable and safe treatment by targeting only the disease-causing signaling pathway while sparing healthy cellular processes.
3Object-affected harmful factors
If IL-17 signaling is blocked to treat autoimmune diseases, then disease progression is halted, but understanding of signaling mechanisms is required
Solution Approach 1:
The patent extracts the critical SEFIR domain interaction interface from the complex IL-17 signaling cascade. By focusing on this specific extracted target, the invention simplifies the therapeutic approach while maintaining effectiveness, reducing the need for comprehensive understanding of the entire complex signaling network.
Data Source
AI summary
A method of treating an IL-17 mediated disease in a subject by administering to the subject a therapeutically effective amount of a of a cell-permeable decoy peptide that competitively inhibits binding of the SEFIR domain of IL-17R to the SEFIR domain of Act1. In particular, it has been determined that the αC helix region of the SEFIR domain of both IL-17R and Act1 plays an important role in the association of IL-17R and Act1. To facilitate cell permeation, the decoy peptide is preferably conjugated to a protein transduction domain. Examples of IL-17 mediated diseases include various human and animal inflammatory and autoimmune diseases such as asthma.