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Title: Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes

Abstract

In this study, antimicrobial peptides or their synthetic mimics are a promising class of potential new antibiotics. Herein we assess the effect of the type of cationic side chain (i.e., guanidino vs. amino groups) on the membrane perturbing mechanism of antimicrobial α-peptide–β-peptoid chimeras. Langmuir monolayers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) were used to model cytoplasmic membranes of both Gram-positive and Gram-negative bacteria, while lipopolysaccharide Kdo2-lipid A monolayers were mimicking the outer membrane of Gram-negative species. We report the results of the measurements using an array of techniques, including high-resolution synchrotron surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial activity to study the molecular mechanisms of peptidomimetic interaction with bacterial membranes. We found guanidino group-containing chimeras to exhibit greater disruptive activity on DPPG monolayers than the amino group-containing analogues. However, this effect was not observed for lipopolysaccharide monolayers where the difference was negligible. Furthermore, the addition of the nitrobenzoxadiazole fluorophore did not reduce the insertion activity of these antimicrobials into both model membrane systems examined, which may be useful for future cellular localization studies.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1227320
Alternate Identifier(s):
OSTI ID: 1225369
Grant/Contract Number:  
W-31-109-Eng-38; AC02-06CH11357; W-31-109-ENG-38; R01 AI073892; W911NF-09-1-378; 09-065902; 09-066098; 10-080907
Resource Type:
Published Article
Journal Name:
Biochimica et Biophysica Acta. Biomembranes
Additional Journal Information:
Journal Name: Biochimica et Biophysica Acta. Biomembranes Journal Volume: 1838 Journal Issue: 10; Journal ID: ISSN 0005-2736
Publisher:
Elsevier
Country of Publication:
Netherlands
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; antimicrobial peptidomimetics; peptide-peptoid chimeras; guanidinium cation; bacterial membrane; phosphatidylglycerol; X-ray scattering

Citation Formats

Andreev, Konstantin, Bianchi, Christopher, Laursen, Jonas S., Citterio, Linda, Hein-Kristensen, Line, Gram, Lone, Kuzmenko, Ivan, Olsen, Christian A., and Gidalevitz, David. Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes. Netherlands: N. p., 2014. Web. doi:10.1016/j.bbamem.2014.05.022.
Andreev, Konstantin, Bianchi, Christopher, Laursen, Jonas S., Citterio, Linda, Hein-Kristensen, Line, Gram, Lone, Kuzmenko, Ivan, Olsen, Christian A., & Gidalevitz, David. Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes. Netherlands. doi:10.1016/j.bbamem.2014.05.022.
Andreev, Konstantin, Bianchi, Christopher, Laursen, Jonas S., Citterio, Linda, Hein-Kristensen, Line, Gram, Lone, Kuzmenko, Ivan, Olsen, Christian A., and Gidalevitz, David. Wed . "Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes". Netherlands. doi:10.1016/j.bbamem.2014.05.022.
@article{osti_1227320,
title = {Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes},
author = {Andreev, Konstantin and Bianchi, Christopher and Laursen, Jonas S. and Citterio, Linda and Hein-Kristensen, Line and Gram, Lone and Kuzmenko, Ivan and Olsen, Christian A. and Gidalevitz, David},
abstractNote = {In this study, antimicrobial peptides or their synthetic mimics are a promising class of potential new antibiotics. Herein we assess the effect of the type of cationic side chain (i.e., guanidino vs. amino groups) on the membrane perturbing mechanism of antimicrobial α-peptide–β-peptoid chimeras. Langmuir monolayers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) were used to model cytoplasmic membranes of both Gram-positive and Gram-negative bacteria, while lipopolysaccharide Kdo2-lipid A monolayers were mimicking the outer membrane of Gram-negative species. We report the results of the measurements using an array of techniques, including high-resolution synchrotron surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial activity to study the molecular mechanisms of peptidomimetic interaction with bacterial membranes. We found guanidino group-containing chimeras to exhibit greater disruptive activity on DPPG monolayers than the amino group-containing analogues. However, this effect was not observed for lipopolysaccharide monolayers where the difference was negligible. Furthermore, the addition of the nitrobenzoxadiazole fluorophore did not reduce the insertion activity of these antimicrobials into both model membrane systems examined, which may be useful for future cellular localization studies.},
doi = {10.1016/j.bbamem.2014.05.022},
journal = {Biochimica et Biophysica Acta. Biomembranes},
number = 10,
volume = 1838,
place = {Netherlands},
year = {2014},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.bbamem.2014.05.022

Citation Metrics:
Cited by: 18 works
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Works referencing / citing this record:

Triangular prism-shaped β-peptoid helices as unique biomimetic scaffolds
journal, May 2015

  • Laursen, Jonas S.; Harris, Pernille; Fristrup, Peter
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms8013

Triangular prism-shaped β-peptoid helices as unique biomimetic scaffolds
journal, May 2015

  • Laursen, Jonas S.; Harris, Pernille; Fristrup, Peter
  • Nature Communications, Vol. 6, Issue 1
  • DOI: 10.1038/ncomms8013