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Polymer-based synthetic mimics of antimicrobial peptides (SMAMPs) are nature-inspired antimicrobial agents. They mimic the properties of antimicrobial peptides (AMPs), which are host-defense peptides found in virtually every organism. This chapter briefly discusses the structure and mechanisms of action of AMPs, and why they are less prone to cause bacterial resistance than traditional antibiotics. We then review the systematic studies that were conducted with poly(methacrylate)-based, nylon-3-based and poly(norbornene)-based SMAMPs: we first discuss how synthetic polymers were designed to emulate the structure and mechanism of AMPs, and then show how important structural parameters like charge, hydrophobicity, molecular weight and counterions affect the antimicrobial and toxicological properties of polymer SMAMPs. We also review important biophysical studies that investigate the interaction of the three families of polymer SMAMPs with biomembranes and synthetic model membranes, and discuss the mechanistic details these studies revealed.

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