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Title: Helical Antimicrobial Sulfono- {gamma} -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 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.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science - Office of Basic Energy Sciences - Scientific User Facilities Division
OSTI Identifier:
1239549
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Journal of Medicinal Chemistry
Additional Journal Information:
Journal Volume: 58; Journal Issue: 11; Journal ID: ISSN 0022-2623
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English

Citation Formats

Li, Yaqiong, Wu, Haifan, Teng, Peng, Bai, Ge, Lin, Xiaoyang, Zuo, Xiaobing, Cao, Chuanhai, and Cai, Jianfeng. Helical Antimicrobial Sulfono- {gamma} -AApeptides. United States: N. p., 2015. Web. doi:10.1021/acs.jmedchem.5b00537.
Li, Yaqiong, Wu, Haifan, Teng, Peng, Bai, Ge, Lin, Xiaoyang, Zuo, Xiaobing, Cao, Chuanhai, & Cai, Jianfeng. Helical Antimicrobial Sulfono- {gamma} -AApeptides. United States. https://doi.org/10.1021/acs.jmedchem.5b00537
Li, Yaqiong, Wu, Haifan, Teng, Peng, Bai, Ge, Lin, Xiaoyang, Zuo, Xiaobing, Cao, Chuanhai, and Cai, Jianfeng. 2015. "Helical Antimicrobial Sulfono- {gamma} -AApeptides". United States. https://doi.org/10.1021/acs.jmedchem.5b00537.
@article{osti_1239549,
title = {Helical Antimicrobial Sulfono- {gamma} -AApeptides},
author = {Li, Yaqiong and Wu, Haifan and Teng, Peng and Bai, Ge and Lin, Xiaoyang and Zuo, Xiaobing and Cao, Chuanhai and Cai, Jianfeng},
abstractNote = {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.},
doi = {10.1021/acs.jmedchem.5b00537},
url = {https://www.osti.gov/biblio/1239549}, journal = {Journal of Medicinal Chemistry},
issn = {0022-2623},
number = 11,
volume = 58,
place = {United States},
year = {Thu Jun 11 00:00:00 EDT 2015},
month = {Thu Jun 11 00:00:00 EDT 2015}
}