WKYMVm Peptide Analog Stability via Beta3-Amino Acid Substitution
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Solution Overview
Problem
The WKYMVm peptide, a potent FPR agonist, has a short in vivo half-life due to rapid decomposition, requiring continuous administration in large doses for therapeutic use.
Innovation Solution
Development of a WKYMVm peptide analog with increased stability in vivo by substituting at least one amino acid residue from Lys, Tyr, or Met with a β3-amino acid residue or a peptoid residue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the WKYMVm peptide is used as a therapeutic agent, then immune activity is effective, but the peptide requires continuous administration in large doses due to rapid decomposition in vivo
Solution Approach 1:
The patent applies parameter changes by substituting specific amino acid residues (Lys, Tyr, or Met) with β3-amino acid residues or peptoid residues in the WKYMVm peptide sequence. This chemical modification changes the peptide's resistance to proteolytic degradation, thereby extending its in vivo half-life from minutes to hours while preserving its FPR agonist activity and immune-enhancing effects
Solution Approach 2:
The patent creates composite peptide structures by combining natural amino acids with non-natural β3-amino acid residues or peptoid residues. This composite approach integrates the immunological activity of the original WKYMVm sequence with the enhanced stability properties of the modified residues, achieving both effective immune activity and prolonged duration of action
2Productivity
If the WKYMVm peptide is administered to achieve therapeutic effect, then neutrophil activation is promoted, but large doses are required due to rapid decomposition
Solution Approach 1:
By modifying the peptide sequence to include β3-amino acid or peptoid residues, the patent changes the degradation rate parameter, allowing lower doses to achieve the same therapeutic effect over extended periods. The modified peptide maintains high neutrophil activation efficiency while reducing the total quantity required for treatment
3Reliability
If continuous administration in large doses is used, then therapeutic effect is maintained, but treatment complexity and cost increase
Solution Approach 1:
The extended half-life achieved through amino acid substitution allows transition from continuous frequent dosing to less frequent dosing regimens. This parameter change in duration of action simplifies the administration complexity while maintaining reliable therapeutic effects throughout the extended dosing interval
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 peptide analog exhibits enhanced stability with a prolonged in vivo degradation half-life and maintains the ability to induce neutrophil activation through FPR activation, effectively promoting innate immune responses.
Implementation Method 1
Formyl peptide receptors (FPR) belong to G protein-coupled receptors involved in chemotaxis found in phagocytic cells such as neutrophils, monocytes, macrophages, and dendritic cells
Data Source
AI summary
The present invention relates to a WKYMVm peptide analog comprising an amino acid sequence of Trp (W)-Lys (K)-Tyr (Y)-Met (M)-Val (V)-D-Met (m), in which at least one amino acid residue selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence is substituted with a β3-amino acid residue or a peptoid residue, and a use thereof. The WKYMVm peptide analogs of the present invention has effects of increasing stability by increasing in vivo degradation half-life and of promoting activation of innate immune responses by neutrophils through activation of formyl peptide receptors, and thus can be effectively used in preventing or treating a disease that is be prevented or treated by formyl peptide receptors, especially an infectious disease or inflammatory disease.