Cyclic enkephalin and dermorphin analogues containing a carbonyl bridge.
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.
Filip
Katarzyna
K
Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093 Poland.
Oleszczuk
Marta
M
Wójcik
Jacek
J
Chung
Nga N
NN
Schiller
Peter W
PW
Pawlak
Danuta
D
Zieleniak
Agnieszka
A
Parcińska
Agnieszka
A
Witkowska
Ewa
E
Izdebski
Jan
J
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
D004723:Endorphins; D004745:Enkephalins; D007202:Indicators and Reagents; D010456:Peptides, Cyclic