Irreversible labelling of the opioid receptors by a melphalan-substituted [Met5]enkephalin-Arg-Phe derivative
| Autor: | Sándor Benyhe, András Z. Rónai, K. Medzihradszky, Ildikó Szatmári, György Orosz, Nana Sartania, Anna Borsodi |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Agonist animal structures Enkephalin medicine.drug_class Stereochemistry Enkephalin Methionine Narcotic Antagonists Guinea Pigs Peptide (+)-Naloxone Biology Binding Competitive Guinea pig Radioligand Assay Opioid receptor hemic and lymphatic diseases medicine Animals Amino Acid Sequence Opioid peptide Receptor Melphalan neoplasms Pharmacology chemistry.chemical_classification Binding Sites Membranes integumentary system Naloxone Brain Affinity Labels Naltrexone Rats Amino Acid Substitution chemistry Receptors Opioid embryonic structures Female |
| Zdroj: | European Journal of Pharmacology. 373:241-249 |
| ISSN: | 0014-2999 |
| Popis: | [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 kappa-binding profile and was a weak kappa-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 microM 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 kappa-opioid receptor. |
| Databáze: | OpenAIRE |
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