title: Investigating the effect of increasing charge density on the hemolytic activity of synthetic antimicrobial polymers.
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.
authors.affiliation: Department of Polymer Science and Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA.
authors.forename: Zoha M
authors.initials: ZM
authors.lastname: Al-Badri
authors.forename: Abhigyan
authors.initials: A
authors.lastname: Som
authors.forename: Sarah
authors.initials: S
authors.lastname: Lyon
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Nelson
authors.forename: Klaus
authors.initials: K
authors.lastname: Nüsslein
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Tew
mesh_terms: D000588:Amines / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013211:Staphylococcus aureus / Q000378:metabolism
chemical_list: D000588:Amines; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008055:Lipids; D010455:Peptides; D011108:Polymers