title: Synthesis of Albicidin Derivatives: Assessing the Role of N-terminal Acylation on the Antibacterial Activity.
abstract: The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium, Xanthomonas albilineans, represents the most prominent member of a new class of antibacterial gyrase inhibitors. It shows remarkable antibacterial activities against Gram-positive and Gram-negative microorganisms. Its unique structure potentially represents a new lead structure for the development of an antibacterial drug. Here we report the synthesis of 14 albicidin derivatives with structural variations at the N-terminus, primarily investigating the effects of variation of cinnamoyl, phenylpropanoyl, and benzoyl residues. Gyrase inhibition in vitro and determination of minimal inhibitory concentrations were assessed in parallel. Activities in a nanomolar range and the importance of N-acylation were demonstrated.
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kerwat
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Grätz
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Kretz
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Seidel
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Kunert
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany.
authors.forename: John B
authors.initials: JB
authors.lastname: Weston
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17. Juni 124, 10623, Berlin, Germany. Suessmuth@chem.TU-Berlin.DE.
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
mesh_terms: D000215:Acylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009930:Organic Chemicals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014974:Xanthomonas / Q000737:chemistry / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D009930:Organic Chemicals; C046156:albicidin
keywords: albicidin; antibacterials; antibiotics; gyrase; para-aminobenzoic acid; peptides