1,2,3‐Triazolium‐Based Cationic Amphipathic Peptoid Oligomers Mimicking Antimicrobial Helical Peptides

Abstract

Amphipathic cationic peptoids (N-substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. Herein we report the first solid-phase synthesis of peptoid oligomers incorporating 1,2,3-triazolium-type side chains and their evaluation against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. Several triazolium-based oligomers, even of short length, selectively kill bacteria over mammalian cells. SEM visualization of S. aureus cells treated with a dodecamer and a hexamer reveals severe cell membrane damage and suggests that the longer oligomer acts by pore formation.

Gramicidin‐S‐Inspired Cyclopeptidomimetics as Potent Membrane‐Active Bactericidal Agents with Therapeutic Potential

“…[9] As a result, the majority of clinical applicable AMPs are used or designed for topical applications only with very few exceptions aimed for systematic applications. [5] To overcome these limitations, many different strategies, including but not limited to structural/ sequence modification, [10][11][12][13] specific delivery system design, [14][15][16][17] "smart" AMPs [18][19][20] and de novo designed antimicrobial peptides/peptidomimetics [21][22][23][24][25][26][27] have been developed to efficiently use AMPs without being hindered by their side-effects. Among these strategies, modification or mimicry of naturally occurring peptides with natural amino acids or unnatural building blocks is an efficient pathway.…”

Helical Antimicrobial Peptide Foldamers Containing Non‐proteinogenic Amino Acids

“…[94] Higher hydrophobization of peptoids does not always equate with potent activity and is dependent on the type of bacteria, such as Escherichia coli, Pseudomonas aeruginosa and S. aureus. [95] Cationic side chains such as the 1,2,3-triazolium-type [96] were used to develop antimicrobial peptoids. Faure and co-workers reported that the 1,2,3-triazolium moiety on various side-chain substituents alters activity and selectivity of the peptoids.…”

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides

“…Following this mimicking trend, Shyam et al prepared a series of 1,2,3-triazolium-based cationic amphipathic peptoid oligomers that mimic antimicrobial helical peptides [ 190 ]. They explored the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids.…”