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Polymers 2011, 3(3), 1512-1532; doi:10.3390/polym3031512

Activity and Mechanism of Antimicrobial Peptide-Mimetic Amphiphilic Polymethacrylate Derivatives

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109, USA
Macromolecular Science and Engineering Center, University of Michigan, 2300 Hayward Ave., Ann Arbor, MI 48109, USA
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA
Author to whom correspondence should be addressed.
Received: 27 July 2011 / Revised: 22 August 2011 / Accepted: 8 September 2011 / Published: 13 September 2011
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Cationic amphiphilic polymethacrylate derivatives (PMAs) have shown potential as a novel class of synthetic antimicrobials. A panel of PMAs with varied ratios of hydrophobic and cationic side chains were synthesized and tested for antimicrobial activity and mechanism of action. The PMAs are shown to be active against a panel of pathogenic bacteria, including a drug-resistant Staphylococcus aureus, compared to the natural antimicrobial peptide magainin which did not display any activity against the same strain. The selected PMAs with 47–63% of methyl groups in the side chains showed minimum inhibitory concentrations of ≤2–31 µg/mL, but cause only minimal harm to human red blood cells. The PMAs also exhibit rapid bactericidal kinetics. Culturing Escherichia coli in the presence of the PMAs did not exhibit any potential to develop resistance against the PMAs. The antibacterial activities of PMAs against E. coli and S. aureus were slightly reduced in the presence of physiological salts. The activity of PMAs showed bactericidal effects against E. coli and S. aureus in both exponential and stationary growth phases. These results demonstrate that PMAs are a new antimicrobial platform with no observed development of resistance in bacteria. In addition, the PMAs permeabilized the E. coli outer membrane at polymer concentrations lower than their MIC values, but they did not show any effect on the bacterial inner membrane. This indicates that mechanisms other than membrane permeabilization may be the primary factors determining their antimicrobial activity.
Keywords: antimicrobials; amphiphilic polymers; host-defense peptides; antibiotic resistance antimicrobials; amphiphilic polymers; host-defense peptides; antibiotic resistance
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Sovadinova, I.; Palermo, E.F.; Urban, M.; Mpiga, P.; Caputo, G.A.; Kuroda, K. Activity and Mechanism of Antimicrobial Peptide-Mimetic Amphiphilic Polymethacrylate Derivatives. Polymers 2011, 3, 1512-1532.

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