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Title: Helical Antimicrobial Sulfono- {gamma} -AApeptides

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 fi rst 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 fl uorescence 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-de fi ned 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.
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Publication Date:
OSTI Identifier:
DOE Contract Number:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Medicinal Chemistry; Journal Volume: 58; Journal Issue: 11
American Chemical Society (ACS)
Research Org:
Argonne National Laboratory (ANL)
Sponsoring Org:
USDOE Office of Science - Office of Basic Energy Sciences - Scientific User Facilities Division
Country of Publication:
United States