Helical Antimicrobial Sulfono-γ-AApeptides.
Basic Information
ID: ALA3576840
Journal: J Med Chem
Title: Helical Antimicrobial Sulfono-γ-AApeptides.
Authors: Li Y, Wu H, Teng P, Bai G, Lin X, Zuo X, Cao C, Cai J.
Abstract: Host-defense peptides (HDPs) such as magainin 2 have emerged as potential therapeutic agents combating antibiotic resistance. Inspired by their structures and mechanism of action, herein we report the first example of antimicrobial helical sulfono-γ-AApeptide foldamers. The lead molecule displays broad-spectrum and potent antimicrobial activity against multi-drug-resistant Gram-positive and Gram-negative bacterial pathogens. Time-kill studies and fluorescence microscopy suggest that sulfono-γ-AApeptides eradicate bacteria by taking a mode of action analogous to that of HDPs. Clear structure-function relationships exist in the studied sequences. Longer sequences, presumably adopting more-defined helical structures, are more potent than shorter ones. Interestingly, the sequence with less helical propensity in solution could be more selective than the stronger helix-forming sequences. Moreover, this class of antimicrobial agents are resistant to proteolytic degradation. These results may lead to the development of a new class of antimicrobial foldamers combating emerging antibiotic-resistant pathogens.
CiteXplore: 26020456
DOI: 10.1021/acs.jmedchem.5b00537
Patent ID: ┄