title: Synthesis of a biological active β-hairpin peptide by addition of two structural motifs.
abstract: The idea of privileged scaffolds - that there seem to be more bioactive compounds found around some structures than others - is well established for small drug molecules, but has little significance for standalone peptide secondary structures whose adaptable shapes escape the definition of a 3D motif in the absence of a protein scaffold. Here, we joined two independent biological functions in a single highly restricted peptide to support the hypothesis that the β-hairpin shape is the common basis of two otherwise unrelated biological recognition processes. To achieve this, the hydrophobic cluster HWX4LV from the decapeptide cyclic hairpin model peptide C1-C10cyclo-CHWEGNKLVC was included in the bicyclic peptide 2. The designed β-hairpin peptide C4-C17, C8-C13bicyclo-KHQCHWECTZGRCRLVCGRSGS (2, Z=citrulline), serves, on the one hand, as a specific epitope for rheumatoid autoantibodies and, on the other hand, shows a not negligible antibiotic effect against the bacterial strain E. coli AS19.
authors.affiliation: Department of Chemistry, Philipps-University Marburg, Hans-Meerwein-Straße 4, 35032 Marburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Fischer
authors.affiliation: Department of Chemistry, Philipps-University Marburg, Hans-Meerwein-Straße 4, 35032 Marburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lamping
authors.affiliation: Department of Neurology, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Gold
authors.affiliation: Department of Neurology, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Röttger
authors.affiliation: Institute for Medical Microbiology and Hospital Hygiene, University Hospital Giessen and Marburg, Hans-Meerwein-Straße, 35033 Marburg, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Brödje
authors.affiliation: Department of Neurology, Philipps-University Marburg, Baldingerstraße, 35043 Marburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.affiliation: Institute for Medical Microbiology, Justus-Liebig University, Biomedical Research Facility Seltersberg, Schubertstraße 81, 35392 Giessen, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Frantz
authors.affiliation: Institute for Medical Microbiology, Justus-Liebig University, Biomedical Research Facility Seltersberg, Schubertstraße 81, 35392 Giessen, Germany.
authors.forename: Mobarak Abu
authors.initials: MA
authors.lastname: Mraheil
authors.affiliation: Institute for Medical Microbiology, Justus-Liebig University, Biomedical Research Facility Seltersberg, Schubertstraße 81, 35392 Giessen, Germany.
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.affiliation: Department of Chemistry, Philipps-University Marburg, Hans-Meerwein-Straße 4, 35032 Marburg, Germany. Electronic address: geyer@staff.uni-marburg.de.
authors.forename: Armin
authors.initials: A
authors.lastname: Geyer
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides
keywords: Disulfides; Filaggrin; NMR spectroscopy; Peptides; β-Hairpin