This paper describes the synthesis and binding profile of a new analog of endomorphin, Cys-endomorphin (C-Y-P-W-F-NH2), to μ- and δ-opioid receptors in rat brain. The new derivative displayed an IC50 of 16 ± 4.7 and > 10,000 nM against the μ-selective [3H] endomorphin-2 and the highly δ-specific [3H] Ile(5,6)-deltorphin II, respectively. Thus, Cys-endomorphin also favors μ- versus δ-opioid binding sites similarly to the parent peptide. The new ligand displayed weak potency with an IC50 of 3,800 nM for [3H] naloxone binding. Even in 10-5 M, the highest concentration tested, Cys-endomorphin was not able to produce 50% inhibition of [3H] naloxone binding in the presence of 100 mM Na+. The data, however, indicated that the agonistic character of endomorphins was retained for the new analog. The difference in the affinity of Cys-endomorphin for peptides versus naloxone supports previous observations with other μ-opioid ligands, namely that disctinct domains of the receptor might participate in the binding of these structurally different compounds.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)