WeightNameValue
1000 Titel
  • Interaction of W-Substituted Analogs of Cyclo-RRRWFW with Bacterial Lipopolysaccharides: the Role of the Aromatic Cluster in Antimicrobial Activity
1000 Autor/in
  1. Keller, Sandro |
  2. Dathe, Margitta |
  3. Bagheri, Mojtaba |
1000 Erscheinungsjahr 2010
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2010-10-21
1000 Erschienen in
1000 Quellenangabe
  • 55(2): 788-797
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028809/ |
  • http://dx.doi.org//10.1128/AAC.01098-10 |
1000 Ergänzendes Material
  • http://aac.asm.org/content/55/2/788/suppl/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The activity of cyclo-RRRWFW (c-WFW) against Escherichia coli has been shown to be modulated by the aromatic motif and the lipopolysaccharides (LPS) in the bacterial outer membrane. To identify interaction sites and to elucidate the mode of c-WFW action, peptides were synthesized by the replacement of tryptophan (W) with analogs having altered hydrophobicity, dipole and quadrupole moments, hydrogen-bonding ability, amphipathicity, and ring size. The peptide activity against Bacillus subtilis and erythrocytes increased with increasing hydrophobicity, whereas the effect on E. coli revealed a more complex pattern. Although they had no effect on the E. coli inner membrane even at concentrations higher than the MIC, peptides permeabilized the outer membrane according to their antimicrobial activity pattern, suggesting a major role of LPS in peptide transport across the wall. For isothermal titration calorimetry (ITC) studies of peptide-lipid bilayer interaction, we used POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline), either alone or in mixtures with 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG), to mimic the charge properties of eukaryotic and bacterial membranes, respectively, as well as in mixtures with lipid A, rough LPS, and smooth LPS as models of the outer membrane of E. coli. Peptide accumulation was determined by both electrostatic and hydrophobic interactions. The susceptibility of the lipid systems followed the order of POPC-smooth LPS >> POPC-rough LPS > POPC-lipid A = POPC-POPG > POPC. Low peptide hydrophobicity and enhanced flexibility reduced binding. The influence of the other properties on the free energy of partitioning was low, but an enhanced hydrogen-bonding ability and dipole moment resulted in remarkable variations in the contribution of enthalpy and entropy. In the presence of rough and smooth LPS, the binding-modulating role of these parameters decreased. The highly differentiated activity pattern against E. coli was poorly reflected in peptide binding to LPS-containing membranes. However, stronger partitioning into POPC-smooth LPS than into POPC-rough LPS uncovered a significant role of O-antigen and outer core oligosaccharides in peptide transport and the permeabilization of the outer membrane and the anti-E. coli activity of the cyclic peptides.
1000 Fachgruppe
  1. Medizin |
  2. Gesundheitswesen |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/S2VsbGVyLCBTYW5kcm8=|https://frl.publisso.de/adhoc/creator/RGF0aGUsIE1hcmdpdHRh|http://orcid.org/0000-0002-5204-6145
1000 Objektart article
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1000 @id frl:6402589.rdf
1000 Erstellt am 2017-05-24T14:13:29.694+0200
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1000 Vgl. frl:6402589
1000 Oai Id
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