title: Synthesis and evaluation of new endomorphin analogues modified at the Pro(2) residue.
abstract: Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Delta(3)Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (DeltaAla) have been used to prepare [Delta(3)Pro(2)]EM-2 (1), [Aze(2)]EM-1 (2), [Aze(2)]EM-2 (3), [3Aze(2)]EM-1 (4), [3Aze(2)]EM-2 (5) and [DeltaAla(2)]EM-2 (6). Binding assays and functional bioactivities for mu- and delta-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.
authors: Dipartimento di Chimica e Tecnologie del Farmaco e Istituto di Chimica Biomolecolare, CNR Sezione di Roma, Sapienza, Università di Roma, P.le A. Moro 5, 00185 Roma, Italy.
authors: Domenica
authors: D
authors: Torino
authors: Adriano
authors: A
authors: Mollica
authors: Francesco
authors: F
authors: Pinnen
authors: Gino
authors: G
authors: Lucente
authors: Federica
authors: F
authors: Feliciani
authors: Peg
authors: P
authors: Davis
authors: Josephine
authors: J
authors: Lai
authors: Shou-Wu
authors: SW
authors: Ma
authors: Frank
authors: F
authors: Porreca
authors: Victor J
authors: VJ
authors: Hruby
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D051381:Rats; D017450:Receptors, Opioid, mu / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D010455:Peptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D001383:Azetidinecarboxylic Acid; D011392:Proline; D000409:Alanine