Andreev, Konstantin11; Bianchi, Christopher11; Laursen, Jonas Striegler1; Citterio, Linda8; Hein-Kristensen, Line9; Gram, Lone8; Kuzmenko, Ivan12; Olsen, Christian Adam1; Gidalevitz, David11
1 Department of Chemistry, Technical University of Denmark2 Organic Chemistry, Department of Chemistry, Technical University of Denmark3 Department of Systems Biology, Technical University of Denmark4 Bacterial Ecophysiology and Biotechnology, Department of Systems Biology, Technical University of Denmark5 National Food Institute, Technical University of Denmark6 Division of Industrial Food Research, National Food Institute, Technical University of Denmark7 Illinois Institute of Technology8 Bacterial Ecophysiology and Biotechnology, Department of Biotechnology and Biomedicine, Technical University of Denmark9 National Institute of Aquatic Resources, Technical University of Denmark10 Argonne National Laboratory11 Illinois Institute of Technology12 Argonne National Laboratory
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.
Biochimica Et Biophysica Acta. Biomembranes, 2014, Vol 1838, Issue 10, p. 2492-2502