The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency Special Issue:Emerging Investigators  

作　　者：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 

机构地区：[1]The Bio21 Institute of Molecular Science and Biotechnology,University of Melbourne,Melbourne,Victoria,Australia [2]ACTV Research group,Melbourne Dental School,Centre for Oral Health Research,University of Melbourne,Melbourne,Victoria,Australia [3]School of Science,RMIT University,Melbourne,Victoria,Australia [4]Melbourne Dental School,Division of Basic and Clinical Oral Sciences,University of Melbourne,Melbourne,Victoria,Australia [5]Department of Biochemistry and Chemistry,La Trobe Institute for Molecular Science,La Trobe University,Melbourne,Victoria,Australia [6]Florey Institute of Neuroscience and Mental Health,University of Melbourne,Melbourne,Victoria,Australia [7]School of Chemistry,University of Melbourne,Melbourne,Victoria,Australia [8]Materials Characterisation and Fabrication Platform,University of Melbourne,Melbourne,Victoria,Australia

出　　处：《Aggregate》2023年第4期195-209,共15页聚集体（英文）

基　　金：The National Health and Medical Research Council,Grant/Award Numbers:APP2018256,APP1142472,APP1158841,APP1185426;Australian Research Council,Grant/Award Numbers:FT210100271,DP210102781,DP160101312,LE200100163;Cancer Council Victoria funding,Grant/Award Number:APP1163284;Australia-China Science and Research Fund-Joint Research Centre on Personal Health Technologies,Grant/Award Number:ACSRF65777;Australian Dental Research Foundation Grant;Pawsey Supercomputing Centre;National Computational Infrastructure;Australian National Fabrication Facility,Grant/Award Number:VictorianNode。

摘　　要：Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional 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 activ-ity 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 solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AMPs over the parental peptide.Our experimental and computationalfindings 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.

关 键 词：AGGREGATION antimicrobial peptide LIPIDATION membrane active peptide 

分 类 号：O62[理学—有机化学]