o-Naphthalenedicarboxaldehyde derivative of 7'-aminonaltrindole as a selective delta-opioid receptor affinity label.
Incorporation of a naphthalene-dialdehyde moiety into the delta antagonist, 6'-aminonaltrindole afforded a potent, selective, irreversible delta-agonist 1. However, flow cytometry studies revealed no time-dependent specific fluorescence, suggesting that both Lys214 and Cys216 at the recognition site are not involved in covalent binding. Molecular simulation studies suggest that compound 1 may form a Schiff base with the epsilon-amino group of Lys214, which could explain its irreversibility and transformation into a delta-agonist through a conformational change of TM5.
Haris
Sarika Prabhu
SP
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Zhang
Yan
Y
Le Bourdonnec
Bertrand
B
McCurdy
Christopher R
CR
Portoghese
Philip S
PS
D000345:Affinity Labels; D009682:Magnetic Resonance Spectroscopy; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000737:chemistry; D009292:Narcotic Antagonists / Q000737:chemistry*; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000345:Affinity Labels; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole