title: Cyclic enkephalin and dermorphin analogues containing a carbonyl bridge.
abstract: Four cyclic enkephalin analogues and four cyclic dermorphin analogues have been synthesized. Cyclization of linear peptides containing basic amino acid residues of various side chain length in position 2 and 5 (enkephalin analogues) or 2 and 4 (dermorphin analogues) was achieved by treatment with bis-(4-nitrophenyl) carbonate to form a urea unit. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse activity was observed, depending on the size of the ring and the location of the urea unit. The conformation of two dermorphin analogues has been studied: one of high activity (IC(50) = 4.15 nM in the GPI assay) and a second of low activity (IC(50) = 6700 nM in the GPI assay). The conformational space of these peptides was examined using the EDMC method. Using data from the NMR spectra, each peptide was described as an ensemble of conformers. Biological activity was discussed in light of the structural data.
authors.affiliation: Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093 Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Filip
authors.forename: Marta
authors.initials: M
authors.lastname: Oleszczuk
authors.forename: Jacek
authors.initials: J
authors.lastname: Wójcik
authors.forename: Nga N
authors.initials: NN
authors.lastname: Chung
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schiller
authors.forename: Danuta
authors.initials: D
authors.lastname: Pawlak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zieleniak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Parcińska
authors.forename: Ewa
authors.initials: E
authors.lastname: Witkowska
authors.forename: Jan
authors.initials: J
authors.lastname: Izdebski
mesh_terms: D000595:Amino Acid Sequence; D004723:Endorphins / Q000138:chemical synthesis*; D004745:Enkephalins / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D004723:Endorphins; D004745:Enkephalins; D007202:Indicators and Reagents; D010456:Peptides, Cyclic