title: The N-terminal nonapeptide of cephaibols A and C: a naturally occurring example of mismatched helical screw-sense control.
abstract: The N-terminal nonapeptide domain of the fungal nonribosomal peptide antibiotics cephaibol A and cephaibol C (AcPheAib4LeuIvaGly- Aib) is reported to adopt a right-handed helical conformation in the crystalline state. However, this conformation is at odds with the left-handed helicity observed in solution in related synthetic oligomers capped with Ac-L-PheAib4 fragments. We report the synthesis of four diastereoisomers of the cephaibol N-terminal nonapeptide, and show by NMR and CD spectroscopy that the peptide containing the chiral amino acids Phe and Leu in the naturally occurring relative configuration exists in solution as an interconverting mixture of helical screw-sense conformers. In contrast, the nonapeptide containing the unnatural relative configuration at Phe and Leu adopts a single, stable helical screw-sense, which is left handed when the N-terminal Phe residue is L and right-handed when the N-terminal Phe residue is D.
authors.affiliation: School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL (UK), Fax: (+44) 161-275-4939.
authors.forename: Ugo
authors.initials: U
authors.lastname: Orcel
authors.forename: Matteo
authors.initials: M
authors.lastname: De Poli
authors.forename: Marta
authors.initials: M
authors.lastname: De Zotti
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clayden
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D007930:Leucine / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D054848:Peptaibols; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D012996:Solutions
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001688:Biological Products; D009842:Oligopeptides; D054848:Peptaibols; D010455:Peptides; D012996:Solutions; C491024:cephaibol A; C491026:cephaibol C; D010649:Phenylalanine; D007930:Leucine
keywords: NMR spectroscopy; conformation; foldamers; peptaibiotics; peptides