Structure-activity relationship in ε-Lysine Peptides : the length effects on antifungal activity

dc.contributor.affiliationSingapore Eye Research Institute; Duke-NUS Graduate Medical School; University of Birmingham; Sandwell and West Birmingham NHS Trust; et al.
dc.contributor.authorAung, Thet Tun
dc.contributor.authorVenktatesh, Mayandi
dc.contributor.authorPeriayah, Mercy Halleluyah
dc.contributor.authorTing, Darren Shu Jeng
dc.contributor.authorWang, Xiu
dc.contributor.authorGoh, Eunice Tze Leng
dc.contributor.authorTun, Sai Bo Bo
dc.contributor.authorHua, Candice Ho Ee
dc.contributor.authorBarathi, Veluchamy Amutha
dc.contributor.authorVerma, Navin Kumar
dc.contributor.authorYue, Wang
dc.contributor.authorTan, Donald Tiang Hwee
dc.contributor.authorChan, Anita Sook Yee
dc.contributor.authorLakshminarayanan, Rajamani
dc.contributor.departmentOphthalmology
dc.contributor.roleMedical and Dental
dc.contributor.trustauthorTing, Darren Shu Jeng
dc.date.accessioned2025-10-21T13:49:30Z
dc.date.available2025-10-21T13:49:30Z
dc.date.issued2025-09-21
dc.description.abstractPolymers 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.
dc.identifier.citationAung 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
dc.identifier.issn1526-4602
dc.identifier.urihttps://westmid.openrepository.com/handle/20.500.14200/8676
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.source.journaltitleBiomacromolecules
dc.subjectOphthalmology
dc.subjectPolymers
dc.titleStructure-activity relationship in ε-Lysine Peptides : the length effects on antifungal activity
dc.typeArticle
dspace.entity.typePublication
oa.grant.openaccessna
rioxxterms.versionNA
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