Synthesis and evaluation of new endomorphin analogues modified at the Pro(2) residue.
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.
Torino
Domenica
D
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.
Mollica
Adriano
A
Pinnen
Francesco
F
Lucente
Gino
G
Feliciani
Federica
F
Davis
Peg
P
Lai
Josephine
J
Ma
Shou-Wu
SW
Porreca
Frank
F
Hruby
Victor J
VJ
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
D009842:Oligopeptides; D010455:Peptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D001383:Azetidinecarboxylic Acid; D011392:Proline; D000409:Alanine