title: Nine-membered cyclodepsitripeptides containing the retroisomeric sequence of ergot peptides.
abstract: In order to examine factors influencing cyclodepsitripeptide formation and stability, three cyclic peptide models containing the alpha-hydroxyacyl-alpha-aminoacylprolyl sequence, corresponding to the peptide lactone cyclo(-Xha-Pro-Xaa-) (Xha = Hiv, Lac; Xaa = Phe, DPhe, DAla), retroisomeric with respect to the ergot oxa-cyclolic peptide moiety, have been considered. Starting from 2,5-dioxomorpholines, aminoacyl incorporation reaction led, through intermediate tetrahedral adducts (aza-cyclols), to the corresponding nine-membered cyclodepsitripeptides cyclo(-Hiv-Pro-DPhe-) 4a, cyclo(-Lac-Pro-DPhe-) 4b, and cyclo (-Hiv-Pro-DAla-) 4c. Compounds 4a-c contain a CONH peptide bond in the nine-membered ring and are stable on standing. Solution conformations of 4a-c, as inferred by NMR spectra and NOE experiments, have been studied. A cis-cis-trans backbone conformation, analogous to that observed in the case of previously studied nine-membered cyclodepsitripeptides containing two proline residues in the ring, is proposed for 4a-c.
authors.affiliation: Department of Pharmaceutical Studies, La Sapienza University, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Calcagni
authors.forename: M
authors.initials: M
authors.lastname: Kajtar-Peredy
authors.forename: G
authors.initials: G
authors.lastname: Lucente
authors.forename: G
authors.initials: G
authors.lastname: Luisi
authors.forename: F
authors.initials: F
authors.lastname: Pinnen
authors.forename: L
authors.initials: L
authors.lastname: Radics
authors.forename: D
authors.initials: D
authors.lastname: Rossi
mesh_terms: D000595:Amino Acid Sequence; D004876:Ergot Alkaloids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism
chemical_list: D004876:Ergot Alkaloids; D009842:Oligopeptides; D010456:Peptides, Cyclic