Accession Number : ADA617344


Title :   Guanidino Groups Greatly Enhance the Action of Antimicrobial Peptidomimetics Against Bacterial Cytoplasmic Membranes


Descriptive Note : Journal article


Corporate Author : ILLINOIS INST OF TECH CHICAGO


Personal Author(s) : Andreev, Konstantin ; Bianchi, Christopher ; Laursen, Jonas S ; Citterio, Linda ; Hein-Kristensen, Line ; Gram, Lone ; Kuzmenko, Ivan ; Olsen, Christian A ; Gidalevitz, David


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a617344.pdf


Report Date : 28 May 2014


Pagination or Media Count : 14


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 mechanism of antimicrobial alpha-peptide Beta-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.


Descriptors :   *ANTIMICROBIAL AGENTS , *BACTERIA , *CYTOPLASM , *MEMBRANES(BIOLOGY) , ANTIBIOTICS , LIPOPOLYSACCHARIDES , X RAY SCATTERING


Subject Categories : Anatomy and Physiology
      Microbiology
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE