Nociceptin/Orphanin FQ(1-13)NH2 analogues modified in the Phe1-Gly2 peptide bond.
The synthesis and pharmacological activity of novel nociceptin/orphanin FQ (N/OFQ) analogues modified in the Phe(1)-Gly(2) peptide bond are reported. The aim of the present work was to elucidate the importance of this peptide bond for the N/OFQ receptor (NOP) interaction. Our study indicates that the first peptide bond in N/OFQ is important but not crucial for interaction with the N/OFQ receptor; for instance, substitution with a methyleneoxy bond generates an agonist derivative just 3-fold less potent than the reference compound.
Guerrini
Remo
R
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, via Fossato di Mortara, 17/19, 44100 Ferrara, Italy. r.guerrini@unife.it
Rizzi
Daniela
D
Zucchini
Marina
M
Tomatis
Roberto
R
Regoli
Domenico
D
Calo'
Girolamo
G
Salvadori
Severo
S
D000818:Animals; D004558:Electric Stimulation; D005998:Glycine / Q000737:chemistry; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D018847:Opioid Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry; D013329:Structure-Activity Relationship; D000097629:Nociceptin
D005998:Glycine; D008024:Ligands; D018847:Opioid Peptides; D010455:Peptides; D010649:Phenylalanine; D000097629:Nociceptin