title: Synthesis and biological activity of [MeTyr1,MeArg7,D-Leu8]-dynorphin A(1-9)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-dynorphin A(1-9)-NH2.
abstract: The opioid activities of [MeTyr1]-Dyn(1-7)-NH2, [MeTyr1,D-Leu8]-Dyn(1-8)-NH2, [MeTyr1,D-Leu8]-Dyn(1-9)-NH2, [MeTyr1,D-Leu8]-Dyn(1-10)-NH2, [MeTyr1,D-Leu8]-Dyn(1-11)-NH2, and [MeTyr1,D-Leu8,12]-Dyn(1-13)-NH2 were examined in the bioassays (guinea pig ileum, mouse vas deferens and rabbit vas deferens). Because [MeTyr1,D-Leu8]-Dyn(1-9)-NH2 showed the most potent opioid activity of the peptides tested, the biological activities of two kinds of Dyn(1-9) analogues, [MeTyr1,MeArg7,D-Leu8]-Dyn(1-9)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-9)-NH2 were determined and compared with those of [MeTyr1,MeArg7,D-Leu8]-Dyn(1-8)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-8)-NHEt in the three bioassays, in the receptor binding assays, and in the mouse tail pinch test after subcutaneous administration. The results suggest that the extension of the C-terminal in the peptide chain of [MeArg7,D-Leu8]-Dyn(1-8)-NH2 analogues by Arg is ineffective for increasing the kappa-opioid activities, kappa-receptor selectivity and/or analgesic effects of the peptides.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: Y
authors.initials: Y
authors.lastname: Arakawa
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Matsunaga
authors.forename: S
authors.initials: S
authors.lastname: Araki
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: K
authors.initials: K
authors.lastname: Yamatsu
authors.forename: S
authors.initials: S
authors.lastname: Tachibana
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D004399:Dynorphins / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu
chemical_list: D000700:Analgesics; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C067204:dynorphin A amide (1-9), Cys(2)-Cys(5)-MeArg(7)-Leu(8)-; C067205:dynorphin A ethylamide (1-9), MeTyr(1)-MeArg(7)-Leu(8)-; D004399:Dynorphins