title: Pharmacodynamic synergy strictly dependent on the co-operative aggregation of enantiomers of cyclic peptides in the bacterial cell membrane.
abstract: The antimicrobial activity of the peptide enantiomers cyclo[D-Tle-D-Lys-D-Tle-L-Ala-D-Tle-L-Ala-D-Tle-L-Ala] and cyclo[L-Tle-L-Lys-L-Tle-D-Ala-L-Tle-D-Ala-L-Tle-D-Ala] against Bacillus megaterium was investigated. Both these peptides showed very low activity in both an agar diffusion assay and a broth microdilution assay. However, when both peptides were present during the experiments a potent inhibition with an IC(50) value of 2 μM was observed. Furthermore, the peptides also showed low hemolytic activity. Neither peptide had any hemolytic activity in concentrations up to 1mM but when erythrocytes were exposed to both peptides a weak hemolytic activity could be observed with a HC(50) value of 316 μM.
authors.affiliation: Department of Neurochemistry, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Danielsson
authors.forename: Katri
authors.initials: K
authors.lastname: Rosenthal-Aizman
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Bergsson
authors.forename: Anders
authors.initials: A
authors.lastname: Undén
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001410:Bacillus megaterium / Q000166:cytology / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic