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Aggregate 2023年第4期4卷 195-209页

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 The Bio21 Institute of Molecular Science and Biotechnology University of MelbourneMelbourneVictoriaAustralia ACTV Research group Melbourne Dental SchoolCentre for Oral Health ResearchUniversity of MelbourneMelbourneVictoriaAustralia School of Science RMIT UniversityMelbourneVictoriaAustralia Melbourne Dental School Division of Basic and Clinical Oral SciencesUniversity of MelbourneMelbourneVictoriaAustralia Department of Biochemistry and Chemistry La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneVictoriaAustralia Florey Institute of Neuroscience and Mental Health University of MelbourneMelbourneVictoriaAustralia School of Chemistry University of MelbourneMelbourneVictoriaAustralia Materials Characterisation and Fabrication Platform University of MelbourneMelbourneVictoriaAustralia

Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of *** mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism *** earlier work showed that two leading AMPs,MSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of *** 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 ***,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 *** 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

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New modular platform based on multi-adjuvanted amphiphilic chitosan nanoparticles for efficient lipopeptide vaccine delivery against group A streptococcus

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Asian Journal of Pharmaceutical Sciences 2022年第3期17卷 435-446页

作者： Abdin Shakirin Mohamad Norpi Muhammad Luqman Nordin Nuraziemah Ahmad Haliza Katas Abdullah Al-Hadi Ahmad Fuaad Asif Sukri Nirmal Marasini Fazren Azmi Centre for Drug Delivery Technology Faculty of PharmacyUniversiti Kebangsaan MalaysiaKuala Lumpur 50300Malaysia Faculty Pharmacy and Health Sciences Universiti Kuala LumpurRoyal College of Medicine PerakPerak 30450Malaysia Faculty of Veterinary Medicine Universiti Malaysia KelantanKelantan 16100Malaysia Department of Chemistry Faculty of ScienceUniversiti MalayaKuala Lumpur 50603Malaysia Universiti Teknologi Mara(UiTM) Bandar Puncak AlamIntegrative Pharmacogenomics Institute(iPROMISE)Selangor 43200Malaysia School of Biomedical Sciences The University of QueenslandSt.Lucia QLD 4072Australia

An effective vaccine against group A streptococcus(GAS)is highly desirable for definitive control of GAS *** the present study,two variants of amphiphilic chitosan nanoparticles-based GAS vaccines were *** vaccines were primarily composed of encapsulated KLH protein(a source of T helper cell epitopes)and lipidated M-protein derived B cell peptide epitope(lipoJ14)within the amphiphilic structure of *** only difference between themwas one of the nanoparticles vaccines received additional surface coating with poly(I:C).The formulated vaccines exhibited nanosized particles within the range of 220–240 *** uptake study showed that nanoparticles vaccine without additional poly(I:C)coating has greater uptake by dendritic cells and macrophages compared to nanoparticles vaccine that was functionalized with poly(I:C).Both vaccines were found to be safe in mice and showed negligible cytotoxicity against HEK293 *** immunization in mice,both nanoparticle vaccines produced high antigen-specific antibodies titres that were regulated by a balanced Th1 and Th2 response compared to physical *** antibodies elicited high opsonic activity against the tested GAS ***,our data demonstrated that amphiphilic chitosan nanoparticles platform induced a potent immune response even without additional inclusion of poly(I:C).

关键词： Amphiphilic chitosan nanoparticles Peptide vaccine lipidation Multi-adjuvanting delivery system Immunogenicity Group A streptococcus

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