Synthesis and binding characteristics of tritiated tipp[Φ], a highly specific and stable delta opioid antagonist

Simon T. Kevin, Géza Tóth, Grazyna Weltrowska, Peter W. Schiller, A. Borsodi

Research output: Contribution to journalArticle

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Abstract

The pseudopeptide H-Tyr-TicΦ[CH2-NH]Phe-Phe-OH (TIPP[Φ]) is a δ opioid antagonist with high δ receptor affinity and unprecedented δ selectivity. TIPP[Φ] was radiolabelled by catalytic tritiation of its precursor [Tyr(3′,5′-I2)1]TIPP[Φ]. The resulting radioligand, [3H]TIPP[Φ], had a specific activity of 1.77 TBq/mmol (47.9 Ci/mmol) and showed high stability against enzymatic degradation. [3H]TIPP[Φ] binding to rat brain membranes was saturable and Scatchard analysis indicated a single binding site with a Kd of 0.98 nM and a Bmax of 105.4 fmol/mg. A study of [3H]TIPP[Φ] binding displacement by various receptor-selective opioids showed the expected rank order of potency (δ ≫ μ > κ). [3H]TIPP[Φ] represents an excellent new radioligand for δ receptor labelling studies in vitro and in vivo.

Original languageEnglish
JournalLife Sciences
Volume56
Issue number10
DOIs
Publication statusPublished - Jan 27 1995

Fingerprint

Narcotic Antagonists
phenylalanylphenylalanine
Opioid Receptors
tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine
Labeling
Opioid Analgesics
Rats
Brain
Binding Sites
Membranes
Degradation

Keywords

  • opioid antagonist
  • radioligand
  • TIPP[Φ]
  • δ opioid receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology

Cite this

Synthesis and binding characteristics of tritiated tipp[Φ], a highly specific and stable delta opioid antagonist. / Kevin, Simon T.; Tóth, Géza; Weltrowska, Grazyna; Schiller, Peter W.; Borsodi, A.

In: Life Sciences, Vol. 56, No. 10, 27.01.1995.

Research output: Contribution to journalArticle

Kevin, Simon T. ; Tóth, Géza ; Weltrowska, Grazyna ; Schiller, Peter W. ; Borsodi, A. / Synthesis and binding characteristics of tritiated tipp[Φ], a highly specific and stable delta opioid antagonist. In: Life Sciences. 1995 ; Vol. 56, No. 10.
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