Quaternized\n1,2,3-Triazolyl Content and Modulation\nPotentiate Antibacterial and Antifungal Activities of Amphipathic\nPeptoids

Bioinspired\nfrom cationic antimicrobial peptides, sequence-defined\ntriazolium-grafted peptoid oligomers (6- to 12-mer) were designed\nto adopt an amphipathic helical polyproline I-type structure. Their\nevaluation on a panel of bacterial strains (Escherichia\ncoli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis), pathogenic fungi (Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus), and\nhuman cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the\nidentification of two heptamers with improved activity to selectively\nfight Staphylococcus aureus pathogens.\nModulation of parameters such as the nature of the triazolium and\nhydrophobic/lipophilic side chains, the charge content, and the sequence\nlength drastically potentiates activity and selectivity. Besides,\nthe ability to block the proinflammatory effect induced by lipopolysaccharide\nor lipoteichoic acid was also explored. Finally, biophysical studies\nby circular dichroism and fluorescence spectroscopies strongly supported\nthat the bactericidal effect of these triazolium-grafted oligomers\nwas primarily due to the selective disruption of the bacterial membrane.