Irreversible labelling of the opioid receptors by a melphalan-substituted [Met5]enkephalin-Arg-Phe derivative

Nana Sartania, Ildikó Szatmári, György Orosz, András Z. Rónai, Kálmán Medzihradszky, Anna Borsodi, Sándor Benyhe

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2 Citations (Scopus)


[Met5]enkephalin-Arg-Phe (Tyr-Gly-Gly-Phe-Met-Arg-Phe) was modified with the methyl esther of melphalan (Mel; 4-bis(2-chloroethyl)amino-L-phenylalanine) and the resulting compounds were studied for their opioid binding properties in guinea pig and rat brain membranes. Three new peptides, with a substitution of a single amino acid, were synthesized (Mel-Gly-Gly-Phe-Met-Arg-Phe, Tyr-Gly-Gly-Mel-Met-Arg-Phe and Tyr-Gly-Gly-Phe-Met-Arg-Mel). In the rat brain, none of these ligands displayed any type specificity, whereas in guinea pig brain membranes the C-terminally modified peptide, Tyr-Gly-Gly-Phe-Met-Arg-Mel ([Mel7]peptide), displayed a κ-binding profile and was a weak κ-opioid-receptor agonist in isolated guinea pig ileum. The effect of sodium ions on [Mel7]peptide competition against [3H]naloxone binding indicated a weak agonist nature of the compound. When guinea pig brain membranes were preincubated with 1-10 μM of [Mel7]peptide, an apparently irreversible inhibition of [3H]naloxone ligand binding was observed. These results suggest that the heptapeptide containing melphalan at the C-terminus can be used as a relatively high affinity irreversible label for the κ-opioid receptor.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number2-3
Publication statusPublished - Jun 4 1999



  • Affinity labelling
  • Brain, guinea pig
  • Ligand binding
  • Melphalan
  • Opioid peptide
  • κ-opioid receptor

ASJC Scopus subject areas

  • Pharmacology

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