Synthesis and evaluation of isothiocyanate-containing derivatives of the δ-opioid receptor antagonist Tyr-Tic-Phe-Phe (TIPP) as potential affinity labels for δ-opioid receptors

D. Y. Maeda, F. Berman, T. F. Murray, J. V. Aldrich

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Derivatives of the δ-opioid receptor-selective peptide antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP) containing an isothiocyanate moiety at the para position of either Phe3 or Phe4 were prepared as potential affinity labels for δ-opioid receptors. The synthesis was accomplished using a general solution-phase synthetic procedure which allows for introduction of affinity labeling groups late in the synthesis of a variety of small peptide substrates. The target peptides and their corresponding amines were then evaluated in radioligand binding experiments using Chinese hamster ovary (CHO)cells expressing δ- and μ-opioid receptors. The peptides [Phe(p-NCS)3]TIPP (2) and [Phe(p-NCS)4]TIPP (4) showed affinity for δ-receptors comparable to the parent compound TIPP (IC50 = 12 and 5 nM, respectively, vs 6 nM for TIPP). Both peptides 2 and 4 were able to inhibit radioligand binding to δ-receptors in a wash-resistant manner at a concentration of 10 nM. Therefore, the peptides [Phe(p-NCS)3]TIPP (2) and [Phe(p-NCS)4]TIPP (4) represent two affinity labels that may prove useful in the study of δ-opioid receptors.

Original languageEnglish (US)
Pages (from-to)5044-5049
Number of pages6
JournalJournal of Medicinal Chemistry
Volume43
Issue number26
DOIs
StatePublished - Dec 28 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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