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This study investigated the optimal number of \u03b5-lysine residues required for antimicrobial activity by comparing peptides with 12, 14, 16, and 18 \u03b5-lysine residues to \u03b5-poly-l-lysine (\u03b5PL). Peptides with 16\u201318 \u03b5-lysine residues showed submicromolar minimum inhibitory concentrations (MICs) against Gram-positive and Gram-negative bacteria while higher MICs for antifungal activity. \u03b5PL demonstrated rapid fungicidal activity by disrupting fungal membranes, inhibiting hyphal growth, and eradicating biofilms in vitro. In rabbit models of corneal epithelial injury, \u03b5PL did not impede wound healing. Topical or intrastromal \u03b5PL significantly reduced fungal burden and disease severity in a rabbit model of Fusarium keratitis. In a mouse model of Candida keratitis, \u03b5PL significantly decreased anterior chamber inflammation and fungal burden compared to voriconazole. These promising findings highlight the potential of \u03b5PL as an antifungal agent for the management of fungal keratitis.<\/jats:p>","DOI":"10.1021\/acs.biomac.5c00907","type":"journal-article","created":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T13:52:02Z","timestamp":1758462722000},"page":"6653-6666","source":"Crossref","is-referenced-by-count":2,"title":["Structure\u2013Activity\nRelationship in \u03b5-Lysine\nPeptides: The Length Effects on Antifungal Activity"],"prefix":"10.1021","volume":"26","author":[{"given":"Thet Tun","family":"Aung","sequence":"first","affiliation":[{"name":"Singapore Eye Research Institute , ,","place":["Singapore, Republic of Singapore, 169856"]},{"name":"Duke-NUS Graduate Medical School , , ,","place":["Singapore, Republic of Singapore, 169857"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayandi","family":"Venktatesh","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute , ,","place":["Singapore, 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of Singapore, 138634"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Yue","sequence":"additional","affiliation":[{"name":"Agency for Science, Technology and Research (A*STAR) , , ,","place":["Singapore, Republic of Singapore, 138634"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald Tiang Hwee","family":"Tan","sequence":"additional","affiliation":[{"name":"Duke-NUS Graduate Medical School , , ,","place":["Singapore, Republic of Singapore, 169857"]},{"name":"Singapore National Eye Centre , ,","place":["Singapore, Republic of Singapore, 168751"]},{"name":"Camden Medical Center , , ,","place":["Singapore, Republic of Singapore, 248649"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita Sook Yee","family":"Chan","sequence":"additional","affiliation":[{"name":"Duke-NUS Graduate Medical School , , ,","place":["Singapore, Republic of Singapore, 169857"]},{"name":"Singapore National Eye Centre , ,","place":["Singapore, 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