Naphthalene dicarboxaldehyde as an electrophilic fluorogenic moiety for affinity labeling: application to opioid receptor affinity labels with greatly improved fluorogenic properties.
To develop ligands with fluorogenic properties amenable for following the kinetics of cross-linking to receptors, a naphthalene dicarboxaldehyde moiety has been attached to an opiate pharmacophore 2 and evaluated in mu-opioid receptors. The fluorescence of the benzo[f]isoindole formed upon cross-linking of mu-opioid receptors by 2 permitted the time-course of covalent bonding to be followed. This demonstrated proof-of-concept suggests the usefulness of naphthalene dicarboxaldehyde-containing affinity labels as kinetic probes.
McCurdy
Christopher R
CR
Department of Medicinal Chemistry, College of Pharmacy, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Le Bourdonnec
Bertrand
B
Metzger
Thomas G
TG
El Kouhen
Rachid
R
Zhang
Yan
Y
Law
Ping Y
PY
Portoghese
Philip S
PS
D000345:Affinity Labels / Q000138:chemical synthesis* / Q000494:pharmacology; D000447:Aldehydes / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000345:Affinity Labels; D000447:Aldehydes; D003432:Cross-Linking Reagents; D009281:Naphthalenes; D017450:Receptors, Opioid, mu