Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

• Published in: Biomacromolecules 2008-11, Vol.9 (11), p.2980-2983
• Main Authors: Gabriel, Gregory J, Madkour, Ahmad E, Dabkowski, Jeffrey M, Nelson, Christopher F, Nüsslein, Klaus, Tew, Gregory N
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides; Applied sciences; Communication; Erythrocytes - drug effects; Exact sciences and technology; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Guanidines - chemistry; Guanidines - pharmacology; Humans; Microbial Sensitivity Tests; Molecular Mimicry; Organic polymers; Physicochemistry of polymers; Polymers - chemistry; Polymers - pharmacology; Polymers with particular properties; Preparation, kinetics, thermodynamics, mechanism and catalysts
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm800855t

Polyguanidinium oxanorbornene (PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents.