Stapled Peptide Design for Antimicrobial Activity and Stability
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Solution Overview
Problem
Current antimicrobial peptides face challenges such as degradation, immunogenicity, specificity issues, and high cost, which hinder their effectiveness in preventing bacterial adhesion and infections, particularly from pathogens like Staphylococcus aureus, and there is a need for agents that can overcome antimicrobial resistance.
Innovation Solution
Stapled peptides are designed with a covalent linkage between specific residues of the 800 peptide derived from the CD9 extracellular domain, enhancing stability and activity by promoting α-helical formation, thereby reducing pathogen adhesion to host cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antimicrobial peptides are used, then antimicrobial activity is achieved, but degradation and immunogenicity occur
Solution Approach 1:
The patent modifies the peptide structure by introducing staples at specific positions (3-7, 10-14, or both) to change the conformational parameters and stabilize the peptide in an alpha-helical structure, thereby improving resistance to degradation while maintaining antimicrobial activity
Solution Approach 2:
The patent creates a composite structure by combining the 800 peptide sequence with staple linkages (covalent bonds between side chains), forming a stapled peptide that integrates the antimicrobial function with enhanced structural stability and protease resistance
2Reliability
If conventional antimicrobial peptides are used, then antimicrobial activity is achieved, but immunogenicity and specificity issues arise
Solution Approach 1:
The patent introduces local modifications at specific positions in the peptide sequence by adding staples at positions 3-7 or 10-14, creating localized structural changes that enhance stability and reduce immunogenicity without compromising the overall antimicrobial function
3Reliability
If conventional antimicrobial peptides are used, then antimicrobial activity is achieved, but high cost and low efficacy occur
Solution Approach 1:
The patent divides the peptide into functional segments by introducing staples at specific positions (3-7 and/or 10-14), which stabilizes the alpha-helical structure and enhances efficacy, allowing for more effective dosing and potentially reducing overall treatment cost
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 stapled peptides demonstrate improved stability and activity, effectively reducing bacterial adhesion and load, including in 3D skin and corneal models, while maintaining non-toxicity and resistance to proteases, thus offering a potent therapeutic option for wound and infection treatment.
Implementation Method 1
Stapled peptides are designed with a covalent linkage between specific residues of the 800 peptide
Implementation Method 2
enhancing stability and activity by promoting α-helical formation
Implementation Method 3
S. aureus has a range of adhesins that allow it to adhere tightly to molecules associated with the host cell surface
Data Source
AI summary
The present invention relates to a peptide for reducing pathogen adhesion. Specifically, a peptide comprising an amino acid sequence having at least 75% sequence identity to SEQ ID NO: 1. The peptide also comprises at least one staple between two or more residues equivalent to residues 3, 7, 10 or 14 of SEQ ID NO: 1.