Format

Send to

Choose Destination
J Med Chem. 2015 Jun 11;58(11):4802-11. doi: 10.1021/acs.jmedchem.5b00537. Epub 2015 May 28.

Helical Antimicrobial Sulfono-γ-AApeptides.

Author information

1
§X-ray Science Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, United States.

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.

PMID:
26020456
DOI:
10.1021/acs.jmedchem.5b00537
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center