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 (US) |
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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 |
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery