41. [Journal Cover] 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 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.

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Lin, B.; Hung, A.; Singleton, W.; Darmawan, K.; Moses, R.; Yao, B.; Wu, H.; Barlow, A.; Sani, M-A; Sloan, A. J.; Hossain, M. A.; Wade, D. J.; Hong, Y.; O’Brien-Simpson; N. M.*; Li, W.*, (2023) The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency, Aggregates, e329, DOI: 10.1002/agt2.329

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42. Genome-Wide Identification and Bioinformatics Analyses of Host Defense Peptides Snakin/GASA in Mangrove Plants

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40. The Overview of Antimicrobial Peptide-Coated Implants Against Oral Bacterial Infections