Selective ligands for opioid receptors: β-Cyclopropylalanyl containing analogs of enkephalin
| Autor: | Alan R. Day, Richard J. Freer, C.S. Liao, Delia Pinon, Natesa Muthukumaraswamy |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Agonist endocrine system Enkephalin Stereochemistry medicine.drug_class Guinea Pigs Ligands Biochemistry Partial agonist Pentapeptide repeat Structure-Activity Relationship chemistry.chemical_compound Vas Deferens Ileum medicine Animals Amino Acid Sequence Opioid peptide Receptor Chemistry Antagonist Enkephalins Rats nervous system Receptors Opioid Biological Assay Indicators and Reagents DADLE Muscle Contraction |
| Zdroj: | International Journal of Peptide and Protein Research. 22:305-312 |
| ISSN: | 0367-8377 |
| DOI: | 10.1111/j.1399-3011.1983.tb02096.x |
| Popis: | The synthesis and resolution of the amino acid β-cyclopropylalanine (Cpr) and its incorporation into four enkephalin analogs is reported. The analogs prepared were: Tyr - l - Cpr - Gly - Phe - Pen (des - COOH - Nle = n - pentylamide = Pen) (l-Cpr2-Pen5-ENK), Tyr-d-Cpr-Gly-Phe-Pen (d-Cpr2-Pen5-ENK), l-Cpr-Tyr-d-Ala-Gly-Phe-Pen (l-Cpr0-d-Ala2-Pen5-ENK) and d-Cpr-Tyr-d-Ala-Gly-Phe-Pen (d-Cpr0-d-Ala2-Pen5-ENK). Each was tested for its ability to inhibit the field stimulated guinea pig ileum (GPI) and rat vas deferens (RVD) and the results compared to the effect d-Ala2-d-Leu5-enkephalin (DADLE) has on the same preparations. The results show that at concentrations up to 10-5m all four analogs, as well as DADLE, are full agonists on the GPI preparation. The concentrations necessary to produce a 50% inhibition of the twitch response were, DADLE, 3.5 °× 10-8m; l - Cpr0-d-Ala2-Pen5-ENK, 6.0 × 10-8m; d-Cpr2-Pen5-ENK, 1.1 × 10-7m; l-Cpr2-Pen5-ENK, 1.2 × 10-6m and d-Cpr0-d-Ala2-Pen5-ENK, > 10-5m. On RVD a different result was observed with only DADLE (1.3 × 10-6m) and l-Cpr0-Pen5-enkephalin (1.8 × 10-6m) showing full agonist activity. d-Cpr2-Pen5-ENK was a partial agonist (29 · 5% inhibition of the twitch at 10-5m) while d-Cpr0-d-Ala2-Pen5-ENK and l-Cpr2-Pen5-ENK did not inhibit the twitch at concentrations up to 10-5m. These compounds which were inactive or of low potency on each preparation were also tested as antagonists. Only d-Cpr2-Pen5-ENK was an antagonist (pA2 = 6.09) versus DADLE on RVD while d-Cpr0-d-Ala2-Pen5-ENK was inactive as an antagonist on both GPI and RVD. d-Cpr2-Pen5-ENK, therefore, represents the first enkephalin analog to be categorized as a mixed agonist-antagonist. |
| Databáze: | OpenAIRE |
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