Side Chain Modifications Change the Binding and Agonist Properties of Endomorphin 2
| Autor: | László Kocsis, Cs. Tömböly, Dauren Biyashev, Zs. Fürst, András Z. Rónai, Imre Lengyel, Mahmoud Al-Khrasani, Anna Borsodi, György Orosz, Géza Tóth |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
Intrinsic activity Enkephalin Protein Conformation medicine.drug_class Stereochemistry Receptors Opioid mu Biophysics (+)-Naloxone Ligands Biochemistry Inhibitory Concentration 50 medicine Animals Structure–activity relationship Rats Wistar Binding site Molecular Biology Binding Sites Dose-Response Relationship Drug Naloxone Chemistry Cell Membrane Brain Biological activity Cell Biology Protein Structure Tertiary Rats Kinetics Models Chemical Mutagenesis Site-Directed μ-opioid receptor Peptides Oligopeptides Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 290:153-161 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.2001.6136 |
| Popis: | Side chain modifications were introduced to endomorphin 2 (E2) to improve its binding properties and biological activity. A number of C-terminal modifications decreased the binding affinity to the mu-opioid receptor and the intrinsic activity in rat brain membranes. The exception was E2-ol, which showed increased binding affinity to MOR and higher potency in stimulating [(35)S]GTPgammaS binding. N-methylation of Phe(3) (MePhe(3)) attenuated the binding affinity and produced a rightward shift of [(35)S]GTPgammaS binding curves. All derivatives had lower intrinsic activity than E2. Some of the modified peptides partially inhibited, while YPF-benzyl-allyl-amide fully inhibited, the E2 or [d-Ala(2),MePhe(4),Gly(5)ol]enkephalin stimulated [(35)S]GTPgammaS binding. Marked differences were found between the results obtained using tritiated E2, tritiated naloxone, and [(35)S]GTPgammaS binding, indicating the possible involvement of multiple binding sites. The data presented demonstrate that the C-terminal amide group has an essential role in the regulation of the binding and the agonist/antagonist properties of E2. |
| Databáze: | OpenAIRE |
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