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

Journal Article · · Biochimica et Biophysica Acta. Biomembranes
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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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE
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
OSTI ID:
1227320
Alternate ID(s):
OSTI ID: 1225369
Journal Information:
Biochimica et Biophysica Acta. Biomembranes, Journal Name: Biochimica et Biophysica Acta. Biomembranes Vol. 1838 Journal Issue: 10; ISSN 0005-2736
Publisher:
ElsevierCopyright Statement
Country of Publication:
Netherlands
Language:
English
Citation Metrics:
Cited by: 53 works
Citation information provided by
Web of Science

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
antimicrobial peptidomimetics
peptide-peptoid chimeras
guanidinium cation
bacterial membrane
phosphatidylglycerol
X-ray scattering