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

Biomacromolecules. 2008 Oct;9(10):2805-10. doi: 10.1021/bm800569x. Epub 2008 Sep 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / chemistry
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Antimicrobial Cationic Peptides / pharmacology*
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Escherichia coli / metabolism
  • Hemolysis / drug effects*
  • Humans
  • Lipids / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Peptides / chemistry
  • Polymers / chemistry
  • Staphylococcus aureus / metabolism


  • Amines
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Lipids
  • Peptides
  • Polymers