title: Synthesis and evaluation of new endomorphin-2 analogues containing (Z)-alpha,beta-didehydrophenylalanine (Delta(Z)Phe) residues.
abstract: New endomorphin-2 (EM-2) analogues incorporating (Z)-alpha,beta-didehydrophenylalanine (Delta(Z)Phe) in place of the native phenylalanine in EM-2 are reported. Tyr-Pro-Delta(Z)Phe-Phe-NH(2) {[Delta(Z)Phe(3)]EM-2} (1), Tyr-Pro-Phe-Delta(Z)Phe-NH(2) {[Delta(Z)Phe(4)]EM-2} (2), and Tyr-Pro-Delta(Z)Phe-Delta(Z)Phe-NH(2) {[Delta(Z)Phe(3,4)]EM-2}(3) have been synthesized, their opioid receptor binding affinities and tissue bioassay activities were determined, and their conformational properties were examined. Compound 2 shows high mu opioid receptor selectivity and mu agonist activity comparable to those of the native peptide. The conformation adopted in solution and in the crystal by N-Boc-Tyr-Pro-Delta(Z)Phe-Phe-NH(2) (8) is reported.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Università di Roma, P.le A.Moro, 00185 Roma, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Torino
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.forename: Francesco
authors.initials: F
authors.lastname: Pinnen
authors.forename: Federica
authors.initials: F
authors.lastname: Feliciani
authors.forename: Gino
authors.initials: G
authors.lastname: Lucente
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Fabrizi
authors.forename: Gustavo
authors.initials: G
authors.lastname: Portalone
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.forename: Shou-Wu
authors.initials: SW
authors.lastname: Ma
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D011957:Receptors, Opioid / Q000819:agonists; D013237:Stereoisomerism
chemical_list: D009842:Oligopeptides; D011957:Receptors, Opioid; C105294:endomorphin 2; D010649:Phenylalanine; C018632:phenyldehydroalanine