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Cyclic enkephalin and dermorphin analogues containing a carbonyl bridge
Author(s) -
Filip Katarzyna,
Oleszczuk Marta,
Wójcik Jacek,
Chung Nga N.,
Schiller Peter W.,
Pawlak Danuta,
Zieleniak Agnieszka,
Parcińska Agnieszka,
Witkowska Ewa,
Izdebski Jan
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.613
Subject(s) - dermorphin , enkephalin , chemistry , bridge (graph theory) , stereochemistry , opioid peptide , opioid , biochemistry , medicine , receptor
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 n M in the GPI assay) and a second of low activity (IC 50 = 6700 n M 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. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.