Investigating the effect of increasing charge density on the hemolytic activity of synthetic antimicrobial polymers.

TitleInvestigating the effect of increasing charge density on the hemolytic activity of synthetic antimicrobial polymers.
Publication TypeJournal Article
Year of Publication2008
AuthorsAl-Badri ZM, Som A, Lyon S, Nelson CF, Nüsslein K, Tew GN
JournalBiomacromolecules
Volume9
Issue10
Pagination2805-10
Date Published2008 Oct
ISSN1526-4602
KeywordsAmines, Anti-Infective Agents, Antimicrobial Cationic Peptides, Chemistry, Pharmaceutical, Drug Design, Erythrocytes, Escherichia coli, Hemolysis, Humans, Lipids, Magnetic Resonance Spectroscopy, Models, Chemical, Peptides, Polymers, Staphylococcus aureus
Abstract

The current study is aimed at investigating the effect of fine-tuning the cationic character of synthetic mimics of antimicrobial peptides (SMAMPs) on the hemolytic and antibacterial activities. A series of novel norbornene monomers that carry one, two, or three Boc-protected amine functionalities was prepared. Ring-opening metathesis polymerization (ROMP) of the monomers, followed by deprotection of the amine groups resulted in cationic antimicrobial polynorbornenes that carry one, two, and three charges per monomer repeat unit. Increasing the number of amine groups on the most hydrophobic polymer reduced its hemolytic activity significantly. To understand the membrane activity of these polymers, we conducted dye leakage experiments on lipid vesicles that mimic bacteria and red blood cell membranes, and these results showed a strong correlation with the hemolysis data.

DOI10.1021/bm800569x
Alternate JournalBiomacromolecules
PubMed ID18816096