Molecular Basis of Selectivity and Activity for the Antimicrobial Peptide Lynronne-1 Informs Rational Design of Peptide with.pdf (881.54 kB)
Molecular basis of selectivity and activity for the antimicrobial Peptide Lynronne-1 informs rational design of Peptide with improved activity
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posted on 2023-06-10, 04:29 authored by Eleanor JayawantEleanor Jayawant, Jack Hutchinson, Dorota Gašparíková, Christine Lockey, Lidón Pruñonosa Lara, Ciaran Guy, Rhiannon L Brooks, Ann M DixonAntibiotic resistance is a significant threat to human health, with natural products remaining the best source for new antimicrobial compounds. Antimicrobial peptides (AMPs) are natural products with great potential for clinical use as they are small, amenable to customization, and show broad-spectrum activities. Lynronne-1 is a promising AMP identified in the rumen microbiome that shows broad-spectrum activity against pathogens such as methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii. Here we investigated the structure of Lynronne-1 using solution NMR spectroscopy and identified a 13-residue amphipathic helix containing all six cationic residues. We used biophysical approaches to observe folding, membrane partitioning and membrane lysis selective to the presence of anionic lipids. We translated our understanding of Lynronne-1 structure to design peptides which varied in the size of their hydrophobic helical face. These peptides displayed the predicted continuum of membrane-lysis activities in vitro and in vivo, and yielded a new AMP with 4-fold improved activity against A. baumannii and 32-fold improved activity against S. aureus.
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Publication status
- Published
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- Published version
Journal
ChemBioChemISSN
1439-4227Publisher
WileyExternal DOI
Issue
14Volume
22Page range
2430-2439Event location
GermanyDepartment affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-08-19First Open Access (FOA) Date
2022-08-19First Compliant Deposit (FCD) Date
2022-08-18Usage metrics
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