title: Helical Antimicrobial Sulfono-γ-AApeptides.
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.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Haifan
authors.initials: H
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Teng
authors.forename: Ge
authors.initials: G
authors.lastname: Bai
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Lin
authors.affiliation: §X-ray Science Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, United States.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zuo
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Cao
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
mesh_terms: D000603:Amino Acids, Sulfur / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D053838:Scattering, Small Angle; D013329:Structure-Activity Relationship
chemical_list: D000603:Amino Acids, Sulfur; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010446:Peptide Fragments; D057786:Peptidomimetics