Ureido group containing cyclic dermorphin(1-7) analogues: synthesis, biology and conformation.
Six cyclic peptides related to dermorphin(1-7) have been synthesized. The synthesis of linear peptides containing diamino acid residues in positions 2 and 4 was carried out on a 4-methylbenzhydrylamine resin, and cyclization 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 opioid agonist activities were observed, depending on the size of the ring. The results were compared with those obtained earlier for 1-4 dermorphin analogues. The conformations of all six dermorphin analogues were studied. The conformational space of the peptides was examined using the electrostatically driven Monte Carlo method. On the basis of NMR data, an ensemble of conformations was obtained for each peptide. The opioid activity profiles of the compounds are discussed in the light of the structural data.
Witkowska
Ewa
E
Peptide Laboratory, Department of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland.
Nowakowski
Michał
M
Oleszczuk
Marta
M
Filip
Katarzyna
K
Ciszewska
Małgorzata
M
Chung
Nga N
NN
Schiller
Peter W
PW
Wójcik
Jacek
J
Izdebski
Jan
J
D000818:Animals; D001681:Biological Assay; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D008297:Male; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D018847:Opioid Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000378:metabolism
D018847:Opioid Peptides; D010456:Peptides, Cyclic; C030058:dermorphin