The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency
Abstract Antimicrobial peptides (AMPs) are potentially powerful alternatives to conventional antibiotics in combating multidrug resistance, given their broad spectrum of activity. They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structu...
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| Format: | Article |
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Wiley
2023-08-01
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| Series: | Aggregate |
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| Online Access: | https://doi.org/10.1002/agt2.329 |
| _version_ | 1797739933053485056 |
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| author | Bruce Lin Andrew Hung William Singleton Kevion K. Darmawan Rachael Moses Bicheng Yao Hongkang Wu Anders Barlow Marc‐Antoine Sani Alastair J. Sloan Mohammed Akhter Hossain John D. Wade Yuning Hong Neil M. O'Brien‐Simpson Wenyi Li |
| author_facet | Bruce Lin Andrew Hung William Singleton Kevion K. Darmawan Rachael Moses Bicheng Yao Hongkang Wu Anders Barlow Marc‐Antoine Sani Alastair J. Sloan Mohammed Akhter Hossain John D. Wade Yuning Hong Neil M. O'Brien‐Simpson Wenyi Li |
| author_sort | Bruce Lin |
| collection | DOAJ |
| description | Abstract Antimicrobial peptides (AMPs) are potentially powerful alternatives to conventional antibiotics in combating multidrug resistance, given their broad spectrum of activity. They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures, resulting in permeability and destruction of target microorganism membranes. Our earlier work showed that two leading AMPs, MSI‐78 (4–20) and pardaxin (1–22), had potent antimicrobial activity against a range of bacteria. It is known that the attachment of moderate‐length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer, inducing membrane curvature, destabilization, and potential leakage. Thus, in this work, we aimed to investigate the antimicrobial activity, oligomerization propensity, and lipid‐membrane binding interactions of a range of N‐terminal lipidated analogs of MSI‐78 (4–20) and pardaxin (1–22). Molecular modeling results suggest that aggregation of the N‐lipidated AMPs may impart greater structural stability to the peptides in solution and a greater depth of lipid bilayer insertion for the N‐lipidated AMPs over the parental peptide. Our experimental and computational findings provide insights into how N‐terminal lipidation of AMPs may alter their conformations, with subsequent effects on their functional properties in regard to their self‐aggregation behavior, membrane interactions, and antimicrobial activity. |
| first_indexed | 2024-03-12T14:05:18Z |
| format | Article |
| id | doaj.art-f6f052e528584d6eabb539cbf923298f |
| institution | Directory Open Access Journal |
| issn | 2692-4560 |
| language | English |
| last_indexed | 2024-03-12T14:05:18Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Aggregate |
| spelling | doaj.art-f6f052e528584d6eabb539cbf923298f2023-08-21T15:03:01ZengWileyAggregate2692-45602023-08-0144n/an/a10.1002/agt2.329The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendencyBruce Lin0Andrew Hung1William Singleton2Kevion K. Darmawan3Rachael Moses4Bicheng Yao5Hongkang Wu6Anders Barlow7Marc‐Antoine Sani8Alastair J. Sloan9Mohammed Akhter Hossain10John D. Wade11Yuning Hong12Neil M. O'Brien‐Simpson13Wenyi Li14The Bio21 Institute of Molecular Science and Biotechnology University of Melbourne Melbourne Victoria AustraliaSchool of Science RMIT University Melbourne Victoria AustraliaACTV Research group, Melbourne Dental School, Centre for Oral Health Research University of Melbourne Melbourne Victoria AustraliaACTV Research group, Melbourne Dental School, Centre for Oral Health Research University of Melbourne Melbourne Victoria AustraliaMelbourne Dental School, Division of Basic and Clinical Oral Sciences University of Melbourne Melbourne Victoria AustraliaDepartment of Biochemistry and Chemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Victoria AustraliaFlorey Institute of Neuroscience and Mental Health University of Melbourne Melbourne Victoria AustraliaMaterials Characterisation and Fabrication Platform University of Melbourne Melbourne Victoria AustraliaThe Bio21 Institute of Molecular Science and Biotechnology University of Melbourne Melbourne Victoria AustraliaMelbourne Dental School, Division of Basic and Clinical Oral Sciences University of Melbourne Melbourne Victoria AustraliaFlorey Institute of Neuroscience and Mental Health University of Melbourne Melbourne Victoria AustraliaFlorey Institute of Neuroscience and Mental Health University of Melbourne Melbourne Victoria AustraliaDepartment of Biochemistry and Chemistry La Trobe Institute for Molecular Science La Trobe University Melbourne Victoria AustraliaThe Bio21 Institute of Molecular Science and Biotechnology University of Melbourne Melbourne Victoria AustraliaThe Bio21 Institute of Molecular Science and Biotechnology University of Melbourne Melbourne Victoria AustraliaAbstract Antimicrobial peptides (AMPs) are potentially powerful alternatives to conventional antibiotics in combating multidrug resistance, given their broad spectrum of activity. They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures, resulting in permeability and destruction of target microorganism membranes. Our earlier work showed that two leading AMPs, MSI‐78 (4–20) and pardaxin (1–22), had potent antimicrobial activity against a range of bacteria. It is known that the attachment of moderate‐length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer, inducing membrane curvature, destabilization, and potential leakage. Thus, in this work, we aimed to investigate the antimicrobial activity, oligomerization propensity, and lipid‐membrane binding interactions of a range of N‐terminal lipidated analogs of MSI‐78 (4–20) and pardaxin (1–22). Molecular modeling results suggest that aggregation of the N‐lipidated AMPs may impart greater structural stability to the peptides in solution and a greater depth of lipid bilayer insertion for the N‐lipidated AMPs over the parental peptide. Our experimental and computational findings provide insights into how N‐terminal lipidation of AMPs may alter their conformations, with subsequent effects on their functional properties in regard to their self‐aggregation behavior, membrane interactions, and antimicrobial activity.https://doi.org/10.1002/agt2.329aggregationantimicrobial peptidelipidationmembrane active peptide |
| spellingShingle | Bruce Lin Andrew Hung William Singleton Kevion K. Darmawan Rachael Moses Bicheng Yao Hongkang Wu Anders Barlow Marc‐Antoine Sani Alastair J. Sloan Mohammed Akhter Hossain John D. Wade Yuning Hong Neil M. O'Brien‐Simpson Wenyi Li The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency Aggregate aggregation antimicrobial peptide lipidation membrane active peptide |
| title | The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency |
| title_full | The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency |
| title_fullStr | The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency |
| title_full_unstemmed | The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency |
| title_short | The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency |
| title_sort | effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency |
| topic | aggregation antimicrobial peptide lipidation membrane active peptide |
| url | https://doi.org/10.1002/agt2.329 |
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