Antibacterial Copolypeptoids with Potent Activity against Drug Resistant Bacteria and Biofilms, Excellent Stability, and Recycling Property

Abstract

The preparation of a type of innovative cationic copolypeptoid antimicrobials containing various hydrophobic moieties that resemble both structure and membrane‐lytic antibacterial mechanism of natural antimicrobial peptides (AMPs) is reported. By finely tuning the hydrophilic/hydrophobic balance, the polypeptoids exhibit a wide spectrum of antibacterial activity against both Gram‐positive bacteria and Gram‐negative bacteria with the lowest minimum inhibitory concentration (MIC) at only 2 µg mL−1, whereas they also show low haemolytic properties. In particular, high selectivity (>128) is achieved from the polymers with butyl moieties. Moreover, the polypeptoids can readily inhibit the formation of biofilms and effectively eradicate the bacteria embedded in the mature biofilms, which is superior to many natural AMPs and vancomycin. Unlike conventional antibiotics, the polypeptoids possess potent activity against drug‐resistant bacteria without visible resistance development after repeated usage. Notably, the polypeptoid antimicrobials not only have inherently fast bactericidal properties and excellent stability against incubation with human plasma, but also show excellent in vivo antibacterial effect. The prepared antimicrobials, coated onto magnetic nanospheres show recycling properties and enhanced antibacterial activity as combined with near‐infrared (NIR)‐induced photothermal antibacterial therapy.

Research Progress in Polypeptoids Prepared by Controlled Ring‐Opening Polymerizations

“…[59] The polypeptoids with long aliphatic spacer between the backbone and side amine groups (Figure 15b) showed the best gene transfection efficiency which outperforms the commercial transfection reagent poly (ethylenimine) by nearly 4 orders of magnitude. Sun et al recently discovered that cationic polypeptoids with sulfonium [58] or primary amine [84] side chains exhibited good antimicrobial activity toward both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus with negligible antibacterial resistance (Figure 15c,d). These cationic polypeptoids also effectively inhibited the formation of bacterial biofilms and eradicate the bacteria embedded in the mature biofilms.…”

“…d) Chemical structures of cationic polypeptoids bearing primary amine side chains, antibacterial activity of the cationic polypeptoids against drug-resistant bacteria, and illustration of recycling of polypeptoids coated with magnetic nanospheres. Adapted with permission [84]. Copyright 2022, John Wiley and Sons.…”

Magnetic Nanoseparation Technology for Efficient Control of Microorganisms and Toxins in Foods: A Review

“…Using ring-opening polymerization and click chemistry, Zhang et al designed a ring-opening peptoid copolymer that mimics AMP-disrupting bacteria. 80 The polypeptide-like antimicrobial agents showed broad-spectrum bactericidal effects against S. aureus, E. coli, Aside from the biorecognition elements described extensively above, various other molecules not covered by these classes also possess affinity and selectivity for pathogens. Compounds from natural sources may be an environmentally friendly, cost-effective, and industrially applicable eco-friendly system.…”

“…A class of peptidomimetic polymers that mimic the structure and function of AMPs has emerged as synthetic antibacterial agents. Using ring-opening polymerization and click chemistry, Zhang et al designed a ring-opening peptoid copolymer that mimics AMP-disrupting bacteria . The polypeptide-like antimicrobial agents showed broad-spectrum bactericidal effects against S.…”

Preparation of a Novel Type of Zwitterionic Polymer and the Antifouling PDMS Coating

“…With a similar backbone structure to polypeptides, polypeptoids exhibit great biocompatibility and bioactivity, which are excellent properties for biomedical applications [ 29 , 30 , 31 ]. In recent years, ring-opening polymerization (ROP) has been used to synthesize polypeptoids with narrow molecular weight dispersions and high molecular weights [ 32 , 33 , 34 ]. In this study, we have developed a facile method for carrying out surface grafting in the aqueous phase with plasma and UV lamps.…”