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, Thomas F. Murray, J. V. Aldrich

Research output: Contribution to journalArticle

14 Citations (Scopus)

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

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phenylalanylphenylalanine
Affinity Labels
Tics
Narcotic Antagonists
Opioid Receptors
Derivatives
Peptides
Cricetulus
Labeling
Inhibitory Concentration 50
Amines
2-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
isothiocyanic acid
Ovary
Cells
Substrates

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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title = "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",
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.",
author = "Maeda, {D. Y.} and F. Berman and Murray, {Thomas F.} and Aldrich, {J. V.}",
year = "2000",
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T1 - 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

AU - Maeda, D. Y.

AU - Berman, F.

AU - Murray, Thomas F.

AU - Aldrich, J. V.

PY - 2000/12/28

Y1 - 2000/12/28

N2 - 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.

AB - 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.

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