HRF-Binding Peptides Inhibit Histamine Secretion
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Solution Overview
Problem
Current treatments for allergic reactions, particularly those mediated by IgE-dependent histamine releasing factor (HRF), lack effective inhibitors to manage histamine and IL-8 secretion, which are key contributors to allergic diseases such as asthma and atopic dermatitis.
Innovation Solution
Development of recombinant deletion forms of HRF that form dimers with enhanced histamine and IL-8 releasing activities, along with novel HRF-binding peptides that inhibit HRF activity, providing a therapeutic approach for allergic diseases by intercepting HRF's passing through cell membranes or binding to (Na, K)ATPase.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HRF-binding peptides are used to inhibit HRF activity, then histamine and IL-8 secretion are reduced, but the mechanism of HRF inducing histamine secretion in basophils remains unclear
Solution Approach 1:
The patent uses HRF-binding peptides as intermediary molecules that specifically bind to HRF to inhibit its activity. These peptides serve as mediators between HRF and its target cells, blocking the interaction without requiring complete understanding of the molecular mechanism. The peptides act as competitive inhibitors that intercept HRF before it can bind to its receptor on basophils.
2Reliability
If deletion forms of HRF are used to enhance histamine releasing activity, then therapeutic efficacy is improved, but protein structure complexity increases
Solution Approach 1:
The patent applies segmentation by creating deletion forms of HRF that remove specific non-essential regions of the protein while retaining the core functional domain responsible for histamine release. This segmentation allows the protein to be divided into functional modules, where only the critical regions are preserved and optimized for therapeutic activity.
Solution Approach 2:
The patent changes structural parameters of the HRF protein by deleting specific amino acid sequences to create variants with enhanced histamine-releasing activity. By modifying parameters such as molecular weight, charge distribution, and conformational flexibility through targeted deletions, the protein's biological activity is optimized while reducing unnecessary structural complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The recombinant deletion forms of HRF and HRF-binding peptides effectively inhibit histamine and IL-8 secretion, offering a promising solution for the prevention and treatment of allergic diseases and potentially malaria, by modulating HRF activity and receptor interactions.
Implementation Method 1
deletion forms of HRF, unlike wild type HRF, have intermolecular disulfide bond, by which dimerization is induced and HRF is activated accordingly
Implementation Method 2
HRF can pass through cell membrane even though it is a hydrophilic protein
Implementation Method 3
HRF receptor is confirmed by yeast two-hybrid assay to be the third cytoplasmic domain (CD3) of (Na,K)ATPase
Implementation Method 4
peptide which i) intercepts HRF's passing through the cell and/or ii) intercepts HRF's binding to (Na, K)ATPase to inhibit histamine secretion
Data Source
AI summary
The present invention relates to IgE-dependent histamine releasing factor (HRF) and HRF-binding peptides, more precisely, deletion forms of HRF which are able to be formed as dimers containing amino acid sequence represented by SEQ ID NO:3, genes encoding thereof and novel HRF-binding peptides having an activity of inhibiting HRF. The deletion forms of HRF which are able to be formed as dimers of the present invention induces intracellular secretion of histamine and IL-8, making an excellent candidate for a drug for inhibiting allergic reaction triggered by HRF and a kit for detecting HRF in serum of an allergy patient. In addition, novel HFR-binding peptides of the present invention bind to HRF to inhibit the actions of HFR, so they can be effectively used for the prevention and the treatment of allergic diseases of animals including asthma and rhinitis or malaria.