TIPP[psi], a highly selective delta ligand.
TIPP[psi] is a new delta-selective opioid peptide antagonist. In the current study, we have explored its selectivity against the mu and kappa receptor subtypes. Against [3H]DPDPE binding, TIPP[psi] is quite potent, with a Ki value of < 1 nM, confirming its potent activity at delta receptors. In contrast, its Ki values against mu 1, mu 2, kappa 1, kappa 2 and kappa 3 binding sites are all > 5 microM. DPDPE also is delta-selective. It labels delta sites > 25-fold more potently than mu 1 receptors and is even more selective against the other subtypes. However, this selectivity does not compare to the delta/mu 1 selectivity of TIPP[psi] which exceeds 15,000. This far higher selectivity, coupled with its antagonist properties, gives TIPP[psi] a number of advantages over previously reported delta-selective compounds. We have utilized these advantages to develop an improved mu 1 binding assay using TIPP[psi].
Visconti
L M
LM
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Standifer
K M
KM
Schiller
P W
PW
Pasternak
G W
GW
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D003342:Corpus Striatum / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism; D006168:Guinea Pigs; D008024:Ligands; D009292:Narcotic Antagonists / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D004745:Enkephalins; D008024:Ligands; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C092721:tyrosyl-tetrahydroisoquinolinecarbonyl-psi(methylamino)phenylalanyl-phenylalanine; D020881:Enkephalin, D-Penicillamine (2,5)-