title: Synthesis, and structural and biological studies of efrapeptin C analogues.
abstract: A series of analogues of efrapeptin C (1), with variations in the central tripeptide epitope (positions 6-8), were prepared by a combination of solid- and solution-phase peptide syntheses. The conformations of the modified compounds 2-6 were investigated by circular-dichroism (CD) spectroscopy to differentiate between 3(10)- and alpha-helical secondary structures. The inhibitory activities of the new compounds towards F(1)-ATPase from E. coli were determined. The modified congeners 3-5 were less active by one order of magnitude compared to 1 (K(i) 10 microM), and 6 was completely inactive. Our experiments demonstrate that the flexible, central tripeptide epitope, comprising positions 6-8 in 1, is crucial for molecular recognition, even slight sequence modifications being hardly tolerated.
authors.affiliation: Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Bielefeld, Germany.
authors.forename: Micha
authors.initials: M
authors.lastname: Jost
authors.forename: Sven
authors.initials: S
authors.lastname: Weigelt
authors.forename: Thomas
authors.initials: T
authors.lastname: Huber
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Majer
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Greie
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Altendorf
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D008958:Models, Molecular; D054848:Peptaibols; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D054848:Peptaibols; D010455:Peptides; C471725:efrapeptin C