Antimicrobial peptide (AMP) is one of the key components of the immune system found in various plants, insect, and animals. The main mechanism is known to attach and destroy the bacterial cells membrane or to penetrate the cell membrane and inhibit cell metabolism.. The cell membrane of the bacteria is known to have a negative charge, thus many AMPs possessed positively charged amino acids. Furthermore, hydrophobic amino acid residues are required to penetrate the hydrophobic bacterial cell phospholipids. To date, there have been active investigations to imitate these peptides and build new artificial systems that complement their disadvantages such as proteolysis, low in vivo efficacy, and hemolytic behavior. Poly(ethylene glycol) (PEG) is the best known polyether widely used in various biomedical applications due to its hydrophilicity, low toxicity and reduced immunogenicity. Similarly, polyether-based polymers synthesized through functional epoxide monomers are anticipated to display similarly high hydrophilicity, flexibility, and biocompatibility. In this study, we design and synthesize a novel AMP mimetic polyethers by using three functional epoxide monomers mimicking natural amino acid. Specifically, azidobutyl glycidyl ether (ABGE) mimicking lysine for cationic charges, isobutyl glycidyl ether (IBGE) mimicking leucine in terms of hydrophobicity, and 1-ethoxyethyl glycidyl ether (EEGE) mimicking serine in regard to hydrophilicity. All monomers are successfully synthesized and copolymerized by anionic ring-opening polymerization (AROP). The prepared AMP-mimetic polyethers in various compositional ratios are carefully characterized through NMR, GPC, and MALDI-TOF. Their biological activities toward diverse bacteria are determined by measuring the minimum inhibitory concentration (MIC) including E. coli, K. pneumoniae, A. baumannii, P. aeruginosa, S. aureus and E. faecium. Moreover, the hemolytic concentration (HC50) toward human red blood cell are assayed to ensure the safety of the prepared AMP-mimetic polyethers. We anticipate the potentials of designer epoxide monomers for the synthesis of functional polyethers toward peptidomimetics.

Antimicrobial peptide mimetic functional polyethers

2019 Spring National Meeting

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