HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Synthesis and pharmacological characterization of a novel, highly potent, peptidomimetic delta-opioid radioantagonist, [3H]Tyr-Tic-(2S,3R)-beta-MePhe-Phe-OH.

Abstract
[(3)H]Tyr-Tic-(2S,3R)-beta-MePhe-Phe-OH (where Tic: 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) with a specific radioactivity of 53.7 Ci/mmol was synthesized and characterized in receptor binding assays at 25 degrees C in rat brain membranes. The specific binding was saturable and displayed high affinity, with a K(D) of 0.16+/-0.005 nM and B(max) of 85.9+/-6.3 fmol/mg protein. NaCl increased its affinity by about 4-fold in membranes of rat brain and Chinese Hamster Ovary Cells stably transfected with the human delta-opioid receptors (hDOR-CHO) showing that the new ligand is an antagonist. The prototypic delta-opioid ligands were much more potent than mu- or kappa-specific ligands in competition assays. The autoradiographic distribution of the binding sites of the new ligand agreed with the known locations of the delta-opioid receptors in rat brain. The unlabeled new ligand was about 7-fold more potent than the parent peptide in competing for the binding sites of [(3)H]Tyr-Tic-(2S,3R)-beta-MePhe-Phe-OH in rat brain membranes. Likewise, the threo-beta-methyl analog was 3.8-fold more potent than the parent compound in antagonizing the effect of DPDPE in the [(35)S]GTPgammaS functional assay in hDOR-CHO membranes. The new, highly potent, conformationally constrained antagonist may be a valuable pharmacological tool in understanding the structural and topographical requirements of peptide ligand binding to the delta-opioid receptors.
AuthorsErika Birkas, Istvan Kertesz, Geza Toth, Lidia Bakota, Karoly Gulya, Maria Szucs
JournalNeuropeptides (Neuropeptides) Vol. 42 Issue 1 Pg. 57-67 (Feb 2008) ISSN: 0143-4179 [Print] Netherlands
PMID18068762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • (3H)Tyr-Tic-(2S,3R)-beta-MePhe-Phe-OH
  • Analgesics, Opioid
  • Oligopeptides
  • Radiopharmaceuticals
  • Receptors, Opioid, delta
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Enkephalin, D-Penicillamine (2,5)-
Topics
  • Analgesics, Opioid (antagonists & inhibitors, pharmacology)
  • Animals
  • Autoradiography
  • Binding Sites
  • Brain Chemistry (drug effects)
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Enkephalin, D-Penicillamine (2,5)- (antagonists & inhibitors, pharmacology)
  • Guanosine 5'-O-(3-Thiotriphosphate) (pharmacology)
  • Humans
  • Male
  • Oligopeptides (chemical synthesis, pharmacology)
  • Radioligand Assay
  • Radiopharmaceuticals (chemical synthesis, pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, delta (antagonists & inhibitors)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: