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Highly potent side‐chain to side‐chain cyclized enkephalin analogues containing a carbonyl bridge: synthesis, biology and conformation
Author(s) -
Pawlak Danuta,
Oleszczuk Marta,
Wójcik Jacek,
Pachulska Maria,
Chung Nga N.,
Schiller Peter W.,
Izdebski Jan
Publication year - 2001
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.303
Subject(s) - side chain , stereochemistry , chemistry , peptide , enkephalin , cyclic peptide , peptide synthesis , amino acid , opioid peptide , combinatorial chemistry , opioid , biochemistry , organic chemistry , receptor , polymer
Six novel cyclic enkephalin analogues have been synthesized. Cyclization of the linear peptides containing basic amino acid residues in position 2 and 5 was achieved by treatment with bis(4‐nitrophenyl)carbonate. It was found that some of the compounds exibit unusually high µ ‐opioid activity in the guinea pig ileum (GPI) assay. The 18‐membered analogue cyclo( N ε , N β ′ ‐carbonyl‐‐Lys 2 ,Dap 5 )enkephalinamide turned out to be one of the most potent µ‐agonists reported so far. NMR spectra of the peptides were recorded and structural parameters were determined. The conformational space was exhaustively examined for each of them using the electrostatically driven Monte Carlo method. Each peptide was finally described as an ensemble of conformations. A model of the bioactive conformation of this class of opioid peptides was proposed. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.