Structure-activity relationship in ε-Lysine Peptides : the length effects on antifungal activity
Aung, Thet Tun Venktatesh, Mayandi Periayah, Mercy Halleluyah Ting, Darren Shu Jeng Wang, Xiu Goh, Eunice Tze Leng Tun, Sai Bo Bo Hua, Candice Ho Ee Barathi, Veluchamy Amutha Verma, Navin Kumar
Aung, Thet Tun
Venktatesh, Mayandi
Periayah, Mercy Halleluyah
Ting, Darren Shu Jeng
Wang, Xiu
Goh, Eunice Tze Leng
Tun, Sai Bo Bo
Hua, Candice Ho Ee
Barathi, Veluchamy Amutha
Verma, Navin Kumar
Citations
Altmetric:
Affiliation
Singapore Eye Research Institute; Duke-NUS Graduate Medical School; University of Birmingham; Sandwell and West Birmingham NHS Trust; et al.
Other Contributors
Publication date
2025-09-21
Subject
Collections
Research Projects
Organizational Units
Journal Issue
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 Fusarium keratitis. In a mouse model of Candida 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.
Citation
Aung TT, Venktatesh M, Periayah MH, Ting DSJ, Wang X, Goh ETL, Tun SBB, Hua CHE, Barathi VA, Verma NK, Yue W, Tan DTH, Chan ASY, Lakshminarayanan R. Structure-Activity Relationship in ε-Lysine Peptides: The Length Effects on Antifungal Activity. Biomacromolecules. 2025 Oct 13;26(10):6653-6666. doi: 10.1021/acs.biomac.5c00907. Epub 2025 Sep 21
Type
Article