Melbourne Dental School - Research Publications

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    The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency Special Issue: Emerging Investigators
    Lin, B ; Hung, A ; Singleton, W ; Darmawan, KK ; Moses, R ; Yao, B ; Wu, H ; Barlow, A ; Marc-Antoine, S ; Sloan, AJ ; Hossain, MA ; Wade, JD ; Hong, Y ; O'Brien-Simpson, NM ; Li, W (WILEY, 2023-08)
    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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    Development and application of Diels-Alder adducts displaying AIE properties
    Gialelis, TL ; Owyong, TC ; Ding, S ; Li, W ; Yu, M ; O'Brien-Simpson, NM ; Zhao, Z ; White, JM ; Yao, B ; Hong, Y (CELL PRESS, 2022-02-16)
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    Recent Applications of Aggregation Induced Emission Probes for Antimicrobial Peptide Studies
    Luu, T ; Li, W ; O'Brien-Simpson, NM ; Hong, Y (WILEY-V C H VERLAG GMBH, 2021-05-03)
    Antimicrobial peptides (AMPs) are being intensively investigated as they are considered promising alternatives to antibiotics where their clinical efficacy is dwindling due to the emergence of antimicrobial resistance (AMR). Accompanying with the development of AMPs, a number of fluorescent probes have been developed to facilitate the understanding the modes of action of AMPs. These probes have been used to monitor the binding process, determine the working mechanism and evaluate the antimicrobial properties of AMPs. In particular, with the recent advance of aggregation-induced emission (AIE) fluorophores, that show many advantageous properties over traditional probes, there is an increasing research interest in using AIE probes for AMP studies. In this review, we give an overview of AMP development, highlight the recent progress of using fluorescence probes in particularly AIE probes in the AMP field and propose the future perspective of developing potent antimicrobial agents to combat AMR.