D-Ala2-Leu5-enkephalin (DALA) was elongated with the methyl ester of melphalan (Mel), a nitrogen mustard on the C-terminus. The new derivative, DALA-Mel-OMe might be a potential affinity label of the opiate receptor. The compound shows high affinity in displacement experiments with an IC50 of 10 nM and 100 nM against 3H-D-Ala2-Leu5-enkephalin and 3H-naloxone, respectively. 10-100 μM of DALA-Mel-OMe causes a significant inhibition of 3H-naloxone binding, which effect can't be reversed by extensive washes. This irreversible blockade is significantly but only partially protected by high concentrations of naloxone and Leu-enkephalin. Our results suggest that DALA-Mel-OMe binds irreversibly to the opiate receptor, but nonspecific labelling also occurs.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)