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 language | English |
|---|---|
| Pages (from-to) | 5044-5049 |
| Number of pages | 6 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 43 |
| Issue number | 26 |
| DOIs | |
| State | Published - Dec 28 2000 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Organic Chemistry
Cite this
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. / Maeda, D. Y.; Berman, F.; Murray, Thomas F.; Aldrich, J. V.
In: Journal of Medicinal Chemistry, Vol. 43, No. 26, 28.12.2000, p. 5044-5049.Research output: Contribution to journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=0034727851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034727851&partnerID=8YFLogxK
U2 - 10.1021/jm000345s
DO - 10.1021/jm000345s
M3 - Article
C2 - 11150176
AN - SCOPUS:0034727851
VL - 43
SP - 5044
EP - 5049
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 26
ER -