title: Synthesis and conformational analysis of efrapeptins.
abstract: The efrapeptin family of peptide antibiotics produced by the fungus Tolypocladium niveum, and the neo-efrapeptins from the fungus Geotrichum candidumare inhibitors of F(1)-ATPase with promising antitumor, antimalaria, and insecticidal activity. They are rich in C(α)-dialkyl amino acids (Aib, Iva, Acc) and contain one β-alanine and several pipecolic acid residues. The C-terminus bears an unusual heterocyclic cationic cap. The efrapeptins C-G and three analogues of efrapeptin C were synthesized using α-azido carboxylic acids as masked amino acid derivatives. All compounds display inhibitory activity toward F(1)-ATPase. The conformation in solution of the peptides was investigated with electronic CD spectroscopy, FT-IR spectroscopy, and VCD spectroscopy. All efrapeptins and most efrapeptin analogues were shown to adopt helical conformations in solution. In the case of efrapeptin C, VCD spectra proved that a 3(10)-helix prevails. In addition, efrapeptin C was conformationally studied in detail with NMR and molecular modeling. Besides NOE distance restraints, residual dipolar couplings (RDC) observed upon partial alignment with stretched PDMS gels were used for the conformational analysis and confirmed the 3(10)-helical conformation.
authors.affiliation: Department of Chemistry, Bielefeld University, P. O. Box 100131, 33501 Bielefeld, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Weigelt
authors.forename: Thomas
authors.initials: T
authors.lastname: Huber
authors.forename: Frank
authors.initials: F
authors.lastname: Hofmann
authors.forename: Micha
authors.initials: M
authors.lastname: Jost
authors.forename: Markus
authors.initials: M
authors.lastname: Ritzefeld
authors.forename: Burkhard
authors.initials: B
authors.lastname: Luy
authors.forename: Christoph
authors.initials: C
authors.lastname: Freudenberger
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Majer
authors.forename: Elemér
authors.initials: E
authors.lastname: Vass
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Greie
authors.forename: Lavinia
authors.initials: L
authors.lastname: Panella
authors.forename: Bernard
authors.initials: B
authors.lastname: Kaptein
authors.forename: Quirinus B
authors.initials: QB
authors.lastname: Broxterman
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Altendorf
authors.forename: Miklós
authors.initials: M
authors.lastname: Hollósi
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D004926:Escherichia coli / Q000201:enzymology; D006999:Hypocreales / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; C012953:efrapeptin; D000251:Adenosine Triphosphatases