Cyclized Peptide Inhibits Hyperpermeability via Sodium Channel Stabilization
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Solution Overview
Problem
Current therapies are ineffective in preventing and treating hyperpermeability of endothelial and epithelial cells, which is a key factor in lung diseases such as acute lung injuries, ARDS, and viral lung diseases, with no standard treatment available for these conditions.
Innovation Solution
A cyclized peptide comprising 7-17 adjacent amino acids, including sequences like CGQRETPEGAEAKPWYC, with no TNF receptor binding activity, is used to prevent and treat hyperpermeability by inhibiting the effects of microbial toxins, reactive oxygen molecules, and viral proteins, thereby stabilizing the epithelial sodium channel and reducing liquid influx into lung tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to treat hyperpermeability, then treatment is provided, but the therapies are ineffective and no standard treatment is available
Solution Approach 1:
The patent introduces a novel peptide compound with specific amino acid sequence (7-17 residues) that cyclizes to form a stable structure. This represents a parameter change from existing therapies to a new molecular entity with optimized structural parameters (cyclization, specific sequence) that achieves both reliability in preventing hyperpermeability and versatility across different lung disease conditions
Solution Approach 2:
The peptide acts as an intermediary substance that mediates between the harmful effects of toxins/reactive oxygen and the endothelial/epithelial cell barrier. It binds to and neutralizes the harmful agents, preventing them from causing hyperpermeability, thus serving as a protective mediator that establishes a reliable treatment mechanism
2Object-affected harmful factors
If microbial toxins and reactive oxygen molecules are present, then cell membranes are damaged and hyperpermeability occurs, but the peptide inhibits these effects
Solution Approach 1:
The peptide is administered to prevent hyperpermeability before it fully develops. It performs preliminary anti-action by binding to toxins and reactive oxygen molecules early, preventing them from forming pores in cell membranes and causing damage. This preemptive approach maintains the reliability of the cell barrier function
Solution Approach 2:
The peptide converts the harmful interaction between toxins and cell membranes into a beneficial interaction where the peptide binds to the toxins, neutralizing their harmful effects. The harmful substances (toxins, reactive oxygen) are transformed from membrane-damaging agents into bound complexes that can be safely eliminated, thus protecting the barrier function
3Reliability
If protein kinase C is activated, then epithelial sodium channel expression is reduced and hyperpermeability develops, but the peptide increases channel expression
Solution Approach 1:
The peptide establishes a positive feedback mechanism that counteracts the harmful feedback loop caused by protein kinase C activation. When toxins activate protein kinase C and reduce sodium channel expression, the peptide intervenes to increase channel expression back to normal levels. This feedback regulation maintains reliable barrier function by correcting deviations caused by pathological activation
Solution Approach 2:
The peptide changes the regulatory parameter of epithelial sodium channel expression from reduced (pathological state) to increased (protective state). By modulating the expression level parameter, the peptide reverses the effect of protein kinase C activation and restores proper barrier function regulation
Data Source
AI summary
A peptide is described, which consists of 7-17 adjacent amino acids and comprises the hexamer TXEXXE, wherein X, X and X can be any natural or non-natural amino acid, wherein the peptide has no TNF receptor binding activity and is cyclized, for the prevention and treatment of hyperpermeability of epithelial cells and endothelial cells.