Nontoxic Membrane‐Active Antimicrobial Arylamide Oligomers

Abstract

Brecheisen für Zellwände: Arylamid‐Oligomere mit amphiphiler Sekundärstruktur greifen die Zellmembran von Bakterien an und zerstören sie. Durch Anhängen verschiedener Substituenten wurden die Gesamtladung, die Hydrophobie und das hydrophobe Moment der Leitverbindung angepasst. Ein Arg‐haltiges Oligomer (siehe Bild) zeigte gute antimikrobielle Aktivität bei geringer Toxizität gegen humane Erythrozyten.

De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers

“…A key feature in the design of these arylamides was a thioether moiety that provided a convenient point of attachment to the basic groups. The thioether also forms intramolecular hydrogen bonds (21,22,(29)(30)(31) to neighboring amides, thereby restricting rotation about the N-C torsional angle between the amide nitrogen and the phenyl ring. However, the molecule retained significant torsional flexibility associated with , the torsional angle connecting the amide carbon and the phenyl group of the isophthalic acid ring.…”

“…A number of studies reported antibiotics designed to follow the mechanism of natural AMPs, for example, peptides composed of ␣-amino acids (15)(16)(17), ␤-amino acids (18,19), peptoids (20), aromatic oligomers (21)(22)(23)(24), and synthetic polymers (25)(26)(27). Previously, we designed a series of arylamide foldamers that showed potential for both activity and selectivity (21).…”

Perspectives on the prevention and treatment of infection for orthopedic tissue engineering applications

“…An example of a naturally occurring antimicrobial peptide is human lactoferrin 1-11 [45]. Synthetic analogues of these naturally-occurring peptides, such as arylamide foldamers, have been synthesized and shown to be effective against bacteria [42,43]. There has been interest in local delivery of AMPs as an alternative to conventional antibiotics.…”

Activity and Mechanism of Antimicrobial Peptide-Mimetic Amphiphilic Polymethacrylate Derivatives

“…This approach was successfully applied to the development of new types of polymer antimicrobials over the last decade, including copolymers of β-lactams [27], polynorbornenes [28], polymethacrylates [29,30], and polystyrenes [31]. Further fine-tuning of the polymers' physiochemical properties by modifying the cationic functionality, amphiphilic balance, and polymer sizes has yielded favorable improvements in antimicrobial activity and selective toxicity to bacteria relative to human red blood cells [30,[32][33][34][35]. In addition to these examples of peptidomimetic polymers, it has been recently reported that several other polymer scaffolds such as oligo(oxazoline)s [36], PEGylated poly(vinyl pyridine)s [37], and polyoxetanes with quaternary ammonium and PEG-like side chains [38] display antibacterial activity and selectivity.…”