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

Abstract

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 mechanismof antimicrobial α-peptide–β-peptoid chimeras. Langmuirmonolayers composed of 1,2-dipalmitoylsn- glycero-3-phosphatidylglycerol (DPPG) were used to model cytoplasmic membranes of both Gram-positive and Gram-negative bacteria,while lipopolysaccharide Kdo2-lipid Amonolayersweremimicking the outer membrane of Gram-negative species.We report the results of themeasurements using an array of techniques, including high-resolution synchrotron surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial activity to study the molecularmechanisms of peptidomimetic interaction with bacterialmembranes.We found guanidino group-containing chimeras to exhibit greater disruptive activity on DPPGmonolayers than the amino group-containing analogues. However, this effect was not observed for lipopolysaccharidemonolayerswhere 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.:
National Institutes of Health (NIH); Danish Council for Independent Research; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1240735
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Biochimica et Biophysica Acta. Biomembranes
Additional Journal Information:
Journal Volume: 1838; Journal ID: ISSN 0005-2736
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
Bacterial membrane; Guanidinium cation; Peptide–peptoid chimeras; Phosphatidylglycerol; X-ray scattering; antimicrobial peptidomimetics

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. United States: 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. United States. 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". United States. doi:10.1016/j.bbamem.2014.05.022.
@article{osti_1240735,
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 = {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 mechanismof antimicrobial α-peptide–β-peptoid chimeras. Langmuirmonolayers composed of 1,2-dipalmitoylsn- glycero-3-phosphatidylglycerol (DPPG) were used to model cytoplasmic membranes of both Gram-positive and Gram-negative bacteria,while lipopolysaccharide Kdo2-lipid Amonolayersweremimicking the outer membrane of Gram-negative species.We report the results of themeasurements using an array of techniques, including high-resolution synchrotron surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial activity to study the molecularmechanisms of peptidomimetic interaction with bacterialmembranes.We found guanidino group-containing chimeras to exhibit greater disruptive activity on DPPGmonolayers than the amino group-containing analogues. However, this effect was not observed for lipopolysaccharidemonolayerswhere 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},
issn = {0005-2736},
number = ,
volume = 1838,
place = {United States},
year = {2014},
month = {1}
}

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