Cyclic Peptides for Vector Ion Channel Regulation
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Solution Overview
Problem
Current therapies lack targeted and effective methods for regulating vector ion channels, particularly in lung tissue, to treat pulmonary edema and associated lung diseases, which impede gas exchange and can be life-threatening.
Innovation Solution
Development of cyclic organic compounds with specific amino acid sequences, including GQRETPEGAEAKPWY, featuring non-natural amino acids and unique ring closures, which activate epithelial sodium channels to regulate ion transport and fluid balance in lung tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional peptide therapies are used to regulate fluid content in alveoli, then some fluid regulation effect is achieved, but the activation of vector ion channels is insufficient and lacks targeted efficacy
Solution Approach 1:
The patent modifies the peptide structure by incorporating non-natural amino acids (ornithine or omega amino acids) and creating unique ring closures between side chains and C-termini, fundamentally changing the molecular parameters to achieve superior ENaC channel activation and targeted fluid regulation in lung tissue
Solution Approach 2:
The invention creates composite peptide structures by combining natural amino acid sequences with non-natural amino acids and specific cyclic modifications, resulting in a hybrid molecule that exhibits enhanced biological activity and selective targeting of epithelial sodium channels
2Reliability
If artificial ventilation is used to ensure oxygen supply in pulmonary edema, then gas exchange is maintained, but the underlying ion transport dysfunction remains untreated
Solution Approach 1:
The cyclic peptide compounds restore the lung tissue's own ion transport function by activating ENaC channels, enabling the biological system to self-regulate fluid balance and gas exchange without continuous mechanical support
3Adaptability or versatility
If existing peptides are used for regulating vector ion channels, then some ion transport modulation is achieved, but targeted activation of epithelial sodium channels in lung tissue is not accomplished
Solution Approach 1:
The patent designs peptides with specific local structural features including ring closures formed by side chain-to-C-terminus bonding and incorporation of non-natural amino acids at specific positions, creating localized molecular characteristics that confer selective affinity for epithelial sodium channels in lung tissue
Data Source
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AI summary
The invention relates to a cyclic organic compound which comprises 16 amino acids or 17 amino acids and has no carboxylic group on the C-terminal end and/or no amino group on the N-terminal end, wherein, if necessary, one of the amino acids is a non-natural amino acid, and wherein the ring closure is formed between a side chain of an amino acid with the C-terminus of another amino acid, or the ring closure is carried out using a non-natural amino acid. The invention also relates to a method for the production thereof and the use thereof for the regulation of vectorial ion channels, the treatment of diseases that are associated with the pulmonary function and the treatment of oedema.