Antimicrobial Peptide Variants Reducing Serum Protein Binding
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Solution Overview
Problem
Existing antimicrobial peptides face challenges in maintaining antimicrobial activity in the presence of serum and blood proteins, leading to reduced bioavailability and effectiveness.
Innovation Solution
Development of variants of an antimicrobial peptide from Arenicola marina with specific alterations at positions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 17, 19, and 21, which exhibit improved antimicrobial activity and reduced protein binding, enhancing bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the parent antimicrobial peptide is used, then antimicrobial activity is achieved, but protein binding to serum and blood proteins occurs which reduces bioavailability
Solution Approach 1:
The patent applies parameter changes by systematically modifying amino acid residues at specific positions (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 17, 19, and 21) of the parent antimicrobial peptide. These sequence variations alter the peptide's chemical properties to reduce protein binding while preserving antimicrobial activity, directly resolving the contradiction between reliability and substance loss.
2Reliability
If the parent antimicrobial peptide is used, then antimicrobial activity is achieved, but serum protein binding reduces effectiveness
Solution Approach 1:
The patent modifies the peptide sequence at multiple positions to change its interaction properties with serum proteins. By altering amino acid composition and structure, the variant peptides exhibit reduced binding affinity to serum and blood proteins, thereby eliminating the harmful binding effect while maintaining antimicrobial function.
3Object-affected harmful factors
If peptide concentration is reduced to improve safety profile, then lower toxicity is achieved, but antimicrobial effectiveness may be compromised
Solution Approach 1:
The patent improves the therapeutic index by modifying peptide sequence parameters to enhance antimicrobial activity. The variant peptides achieve potent antimicrobial effects at lower concentrations, allowing effective treatment while maintaining a favorable safety profile with reduced toxicity compared to the parent peptide.
Data Source
AI summary
The present invention relates to variants of a parent antimicrobial peptide. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.