Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.776012
Title: Lipid topography and lytic peptides : a lipocentric model for pore-forming antimicrobial peptides
Author: Paterson, David James
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2015
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Abstract:
Linear cationic antimicrobial peptides are a diverse family of membrane-active peptides, linked by physiochemical characteristics that induce membrane disruptive effects, including the formation of membrane spanning pores. They offer potential development as novel antimicrobial therapeutics, due to their high potency and evidenced resistance to bacterial drug resistance mechanisms. Complex lipid-peptide interactions are believed to govern their pore formation activity, and their mechanism of selectivity between prokaryotic and eukaryotic cells. Some peptides (e.g. magainin) show a high degree of selectivity for bacterial cells, while some (e.g. melittin) target bacterial and mammalian cells indiscriminately. Within this report, high-throughput microfluidics is used to investigate the pore formation capabilities, of selective and non-selective antimicrobial peptides, within biomimetic vesicles representing both bacterial and mammalian cells. Microfluidics offers precise control over the exposure of lipid membranes to antimicrobial peptides, allowing the pore-formation process to be elucidated in greater detail than conventional techniques. A new model for their mechanism of action is proposed, where lipid topography and lipid-peptide steric interactions exert influence over both pore formation and the selectivity mechanism. The model has potential to inform the rational drug design of future antimicrobial agents, using linear cationic antimicrobial peptides as a template.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.776012  DOI: Not available
Keywords: Q Science (General) ; QC Physics ; QD Chemistry
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