Structure–Activity Relationship in ε-Lysine Peptides: The Length Effects on Antifungal Activity

Polymers with multiple ε-lysine residues exhibit excellent antibacterial activity and membrane selectivity for bacteria and fungi. This study investigated the optimal number of ε-lysine residues required for antimicrobial activity by comparing peptides with 12, 14, 16, and 18 ε-lysine residues to ε-poly-l-lysine (εPL). Peptides with 16-18 ε-lysine residues showed submicromolar minimum inhibitory concentrations (MICs) against Gram-positive and Gram-negative bacteria while higher MICs for antifungal activity. εPL demonstrated rapid fungicidal activity by disrupting fungal membranes, inhibiting hyphal growth, and eradicating biofilms in vitro. In rabbit models of corneal epithelial injury, εPL did not impede wound healing. Topical or intrastromal εPL significantly reduced fungal burden and disease severity in a rabbit model of <i>Fusarium</i> keratitis. In a mouse model of <i>Candida</i> keratitis, εPL significantly decreased anterior chamber inflammation and fungal burden compared to voriconazole. These promising findings highlight the potential of εPL as an antifungal agent for the management of fungal keratitis.

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Publication Details

Journal
Biomacromolecules
Published
2025-09-21
DOI
https://doi.org/10.1021/acs.biomac.5c00907
Primary Topic
Antimicrobial Peptides and Activities
Type
article
Field-Weighted Citation Impact
0.00
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article

Structure–Activity Relationship in ε-Lysine Peptides: The Length Effects on Antifungal Activity

Mercy Halleluyah Periayah, Darren Shu Jeng Ting, Thet Tun Aung, Rajamani Lakshminarayanan et al.
Biomacromolecules
Antimicrobial Peptides and Activities
article

Structure–Activity Relationship in ε-Lysine Peptides: The Length Effects on Antifungal Activity

Mercy Halleluyah Periayah, Darren Shu Jeng Ting, Thet Tun Aung, Rajamani Lakshminarayanan, Veluchamy A. Barathi, Eunice Tze Leng Goh, Anita Sook Yee Chan, Candice Ho Ee Hua, Sai Bo Bo Tun, Xiu Jun Wang, Navin Kumar Verma, Yue Wang, Donald Tan, Mayandi Venktatesh
article en

Abstract

Polymers with multiple ε-lysine residues exhibit excellent antibacterial activity and membrane selectivity for bacteria and fungi. This study investigated the optimal number of ε-lysine residues required for antimicrobial activity by comparing peptides with 12, 14, 16, and 18 ε-lysine residues to ε-poly-l-lysine (εPL). Peptides with 16-18 ε-lysine residues showed submicromolar minimum inhibitory concentrations (MICs) against Gram-positive and Gram-negative bacteria while higher MICs for antifungal activity. εPL demonstrated rapid fungicidal activity by disrupting fungal membranes, inhibiting hyphal growth, and eradicating biofilms in vitro. In rabbit models of corneal epithelial injury, εPL did not impede wound healing. Topical or intrastromal εPL significantly reduced fungal burden and disease severity in a rabbit model of <i>Fusarium</i> keratitis. In a mouse model of <i>Candida</i> keratitis, εPL significantly decreased anterior chamber inflammation and fungal burden compared to voriconazole. These promising findings highlight the potential of εPL as an antifungal agent for the management of fungal keratitis.

BiomacromoleculesVol. 26(10)
Agency for Science, Technology and Research (SG), National Skin Centre (SG), University of Nottingham (GB), Yong In University (KR), National University of Singapore (SG), Nanyang Technological University (SG), American Association of Colleges of Pharmacy (US), Singapore National Eye Center (SG), Sandwell & West Birmingham Hospitals NHS Trust (GB), Department of Health and Aged Care (AU), BC Platforms (Finland) (FI), Institut thématique Immunologie, inflammation, infectiologie et microbiologie (FR), Northwest Eye Surgeons (US), Eye & Retina Surgeons (SG), Society for Academic Emergency Medicine (US), Singapore Eye Research Institute (SG), Birmingham and Midland Eye Centre (GB), Duke-NUS Medical School (SG), Academic Dermatology Associates (US), Tianjin Medical University Eye Hospital (CN), A*STAR Graduate Academy (SG), Tianjin Medical University (CN), University of Birmingham (GB)
Openalex Percentile: Top 76%
Antimicrobial Peptides and Activities
DOISourceOpenAlex
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