Structure-activity study of the ORL1 antagonist Ac-Arg-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH2.
The structure-activity requirements of the ORL1 antagonist Ac-Arg-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH(2) 4 were investigated by varying the position, structure, and charge of the Arg residues. Attempts to abridge the peptide by removal of the Arg, D-Cha, and D-p-ClPhe residues abolished affinity for the ORL1 receptor, whereas deletion of the acetamido N-terminus maintained receptor affinity and selectivity. This series of analogues has provided an improved potent and selective ORL1 receptor antagonist, Ac-Cit-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH(2).
Van Cauwenberghe
Sylvia
S
Eenheid Organische Chemie, Vrije Universiteit Brussel, 2, Pleinlaan, B-1050, Brussels, Belgium.
Simonin
Frédéric
F
Cluzeau
Jérôme
J
Becker
Jérôme A J
JA
Lubell
William D
WD
Tourwé
Dirk
D
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D019556:COS Cells; D006224:Cricetinae; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D009292:Narcotic Antagonists; D011869:Radioligand Assay; D011957:Receptors, Opioid; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000094942:Nociceptin Receptor