Structure-Activity Relationship in ε-Lysine Peptides: The Length Effects on Antifungal Activity
Thet Tun Aung1,2, Mayandi Venktatesh1,2, Mercy Halleluyah Periayah1,2
1Ocular Anti-Infectives and Inflammation, Singapore Eye Research Institute, Singapore 169856 Republic of Singapore.
Biomacromolecules
|September 21, 2025
Summary
Poly-L-lysine (εPL) shows potent antimicrobial and antifungal properties. Studies indicate εPL is effective against fungal keratitis, offering a promising therapeutic option for eye infections.
Area of Science:
- Biochemistry
- Microbiology
- Ophthalmology
Background:
- Polymers with multiple ε-lysine residues possess antibacterial and antifungal properties.
- Understanding the optimal number of ε-lysine residues is crucial for antimicrobial efficacy.
Purpose of the Study:
- To determine the optimal number of ε-lysine residues for antimicrobial activity.
- To evaluate the efficacy of ε-poly-L-lysine (εPL) against fungal keratitis in preclinical models.
Main Methods:
- Synthesized and compared peptides with varying ε-lysine residues (12, 14, 16, 18) and εPL.
- Assessed minimum inhibitory concentrations (MICs) against bacteria and fungi.
- Evaluated εPL in rabbit models of Fusarium keratitis and mouse models of Candida keratitis.
Main Results:
- Peptides with 16-18 ε-lysine residues exhibited submicromolar MICs against bacteria.
- εPL demonstrated rapid fungicidal activity, disrupting fungal membranes and inhibiting growth in vitro.
- εPL treatment reduced fungal burden and disease severity in rabbit and mouse keratitis models, without impeding wound healing.
Conclusions:
- εPL shows significant potential as an antifungal agent for managing fungal keratitis.
- The study highlights εPL's efficacy in preclinical models, suggesting its therapeutic value.
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