Tryptophan replacement in the nociceptin/orphanin FQ receptor ligand Ac-RYYRWK-NH2.
In the present study we describe the in vitro pharmacological characterization of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) ligand Ac-RYYRWK-NH2 and the synthesis and biological evaluation of 13 Trp5 substituted Ac-RYYRWK-NH2 analogs. Results indicate that Ac-RYYRWK-NH2 behaves as a highly potent and selective partial agonist at the NOP receptors and that the whole indole moiety of the Trp5 side chain is not required, being a phenyl-ethyl side chain already sufficient for maintaining high potency.
Carra'
G
G
Section of Pharmacology and Neuroscience Centre, Department of Experimental and Clinical Medicine, University of Ferrara, 44100 Ferrara, Italy.
Calo'
G
G
Spagnolo
B
B
Guerrini
R
R
Arduin
M
M
Marzola
E
E
Trapella
C
C
Regoli
D
D
Salvadori
S
S
D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D018847:Opioid Peptides / Q000819:agonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry*; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D000097629:Nociceptin
D024322:Amino Acids, Aromatic; D009842:Oligopeptides; D018847:Opioid Peptides; D014364:Tryptophan; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C404152:CAM 6369