Bactericidal Peptidomimetic Polyurethanes with Remarkable Selectivity against Escherichia coli

Abstract

The increasing incidence of drug-resistant strains of bacteria necessitates the development of new classes of antimicrobials. Host defense peptides, also known as antimicrobial peptides, are promising in this regard but have several drawbacks. Herein, we show that peptidomimetic polyurethanes with pendant functional groups that mimic lysine and valine amino acid residues have high antibacterial activity against Gram negative Escherichia coli, yet are less effective against Gram positive Staphylococcus aureus. All the polyurethanes designed in this study display high bactericidal activity against E. coli, whereas the polyurethanes with high concentrations of lysine mimicking functional groups display minimal cytotoxicity toward mammalian cells. Control experiments with pexiganan, an analogue of the host defense peptide magainin, showed that the polyurethanes described here have high bactericidal activity, while having comparable hemocompatibility and lower mammalian cell toxicity. Overall, the results point to an encouraging new class of peptidomimetic synthetic polymers with selective bactericidal activity to E. coli and low mammalian cell toxicity.

Biomimetic antimicrobial polymers: recent advances in molecular design

“…The majority of the synthetic antimicrobial polymers are non-biodegradable, which could limit their application due to possible long-term toxicity in vivo, even if they appear to be non-toxic by shortterm in vitro assays. 98,99 Biodegradable antimicrobial polymers based on polyesters, 99,100 polyurethanes, 101,102 polycarbonates 59,60 and networks cross-linked with acetal functionality 103 have been reported to fill this gap. These polymers are hydrolytically or enzymatically cleaved at random sites along the backbone, thus giving a degradation profile that is controlled by the chemical structure of the linkages and the solvent accessibility of the microenvironment.…”

Modification of narrow‐spectrum peptidomimetic polyurethanes with fatty acid chains confers broad‐spectrum antibacterial activity

“…The bactericidal peptidomimetic polyurethane (PU‐1) was synthesized according to our previous report . Briefly, a diol monomer that contains a Boc‐protected amine pendant group was polymerized with HDI at room temperature in dichloromethane catalyzed by tin(II) octoate.…”

“…We previously reported a series of bactericidal peptidomimetic polyurethanes based on a library of N ‐substituted diol monomers . These bactericidal polyurethanes are narrow‐spectrum antimicrobial agents effective against Gram‐negative bacteria such as E. coli , but not against Gram‐positive bacteria such as S. aureus .…”

“…We previously reported a series of bactericidal peptidomimetic polyurethanes based on a library of N ‐substituted diol monomers . These bactericidal polyurethanes are narrow‐spectrum antimicrobial agents effective against Gram‐negative bacteria such as E. coli , but not against Gram‐positive bacteria such as S. aureus . In the present work, the chemical structure of one of these polyurethanes peptidomimetic antimicrobial polyurethanes was modified by amidation using different fatty acids, with the aim of understanding the correlation between the polymer structure and its antimicrobial properties.…”

<p>Development and Study of Biocompatible Polyurethane-Based Polymer-Metallic Nanocomposites</p>

“…The interaction between the cells and the surface depends on the surface charge, while the character of the sorption forces could be determined by the chemical composition of the cells and of the surface (in our case by the polymer nanocomposites). 44…”