Synthesis and binding characteristics of [3H] H-Tyr-Ticψ[CH2-NH] Cha-Phe-OH, a highly specific and stable δ-opioid antagonist

Ildikó Szatmári, Géza Tóth, István Kertész, Peter W. Schiller, Anna Borsodi

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Abstract

Substitution of the Phe3 aromatic ring in H-Tyr-Ticψ[CH2-NH]Phe-Phe-OH with cyclohexylalanine (Cha) has been reported to result in a compound, H-Tyr-Ticψ[CH2-NH]Cha-Phe-OH (TICP[ψ]), showing substantially increased δ-opioid antagonist potency and high δ selectivity. TICP[ψ] was radiolabeled by catalytic tritiation of its precursor Tyr(3',5'-I2)1TICP[ψ]. Binding characteristics of the new tritiated pseudopeptide were determined using the radioligand binding assay in rat brain membranes. On the basis of the results of saturation binding studies performed at 25°C, an equilibrium dissociation constant (K(d)) of 0.35 nM and a receptor density (B(max)) of 112 fmol/mg protein were calculated. This new tritiated ligand exhibits high affinity for δ-opioid receptors, whereas its binding to μ and κ receptors is weak. A study of [H3]TICP[ψ] binding displacement by various receptor-selective opioids showed the following rank order of potency: δ > κ = μ. These receptor binding characteristics of the ligand, together with its high specific radioactivity (41.3 Ci/mmol) and stability, makes it a useful tool for labeling δ-opioid receptors, both in vitro and in vivo. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1079-1083
Number of pages5
JournalPeptides
Volume20
Issue number9
DOIs
Publication statusPublished - Sep 1 1999

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Keywords

  • Conformational restriction
  • Opioid receptors
  • Radioligand binding
  • δ-Opioid antagonist peptides

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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