Endomorphin-1 Analogues Containing β-Proline Are μ-Opioid Receptor Agonists and Display Enhanced Enzymatic Hydrolysis Resistance
| Autor: | Fabio Sgarzi, Santi Spampinato, Ahmed R. Qasem, Giuliana Cardillo, Luca Gentilucci |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
Proline medicine.drug_class Stereochemistry Receptors Opioid mu Cathepsin A Peptide Carboxypeptidases CD13 Antigens In Vitro Techniques Binding Competitive Radioligand Assay chemistry.chemical_compound Opioid receptor Drug Discovery Cyclic AMP Tumor Cells Cultured medicine Animals Chymotrypsin Receptor chemistry.chemical_classification Tetrapeptide Chemistry Hydrolysis Brain Endomorphin-1 Stereoisomerism Rats Amino acid DAMGO Biochemistry Molecular Medicine Oligopeptides |
| Zdroj: | Journal of Medicinal Chemistry. 45:2571-2578 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm011059z |
| Popis: | In this paper we describe the synthesis and affinity toward the mu-opioid receptor of some tetrapeptides obtained from endomorphin-1, H-Tyr-Pro-Trp-Phe-NH(2) (1), by substituting each amino acid in turn with its homologue. The ability to bind mu-opioid receptors depends on the beta-amino acid, and in particular 4, which contains beta-L-Pro, has a K(I) in the nanomolar range. The peptides 4 and 5 are significantly more resistant to enzymatic hydrolysis than 1. The same compounds, as well as the mu-opioid receptor agonist DAMGO, produced a concentration-dependent inhibition of forskolin-stimulated cyclic AMP formation, thus behaving as mu-opioid agonists. These features suggest that this novel class of endomorphin-1 analogues may represent suitable candidates for the in vivo investigation as potential mu-opioid receptor agonists. |
| Databáze: | OpenAIRE |
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