The recent discovery of some agonists at opioid receptor lacking the protonatable amino group [1], leads to the re-discussion of the importance of ionic interactions in stabilizing the ligand-receptor complex and in activating signal transduction. Recently, we have synthesized cyclic analogues of endomorphin-1 (EM-1), containing different Xaa5 bridges between Tyr1 and Phe4. These lipophilic, cyclic EM-1 analogues displayed good affinities for MORs, allowing to hypothesize that they could interact with the receptor by a peculiar, alternative fashion, which has been investigated by Molecular Docking. The docking results gave a detailed description of ligand binding interactions and their electronic properties. The comparison with the agonist JOM-6 binding mode [50,51] indicated that the cyclic EM-1 analogues have an alternative interaction mechanism, still maintaining the ability to activate the receptor.

Investigation on MOR receptor activation by atypical mechanisms

GENTILUCCI, LUCA;DE MARCO, ROSSELLA;SPAMPINATO, SANTI MARIO;BEDINI, ANDREA
2008

Abstract

The recent discovery of some agonists at opioid receptor lacking the protonatable amino group [1], leads to the re-discussion of the importance of ionic interactions in stabilizing the ligand-receptor complex and in activating signal transduction. Recently, we have synthesized cyclic analogues of endomorphin-1 (EM-1), containing different Xaa5 bridges between Tyr1 and Phe4. These lipophilic, cyclic EM-1 analogues displayed good affinities for MORs, allowing to hypothesize that they could interact with the receptor by a peculiar, alternative fashion, which has been investigated by Molecular Docking. The docking results gave a detailed description of ligand binding interactions and their electronic properties. The comparison with the agonist JOM-6 binding mode [50,51] indicated that the cyclic EM-1 analogues have an alternative interaction mechanism, still maintaining the ability to activate the receptor.
2008
Book of abstracts
12
12
G. Bombieri; R. Artali; L. Gentilucci; R. De Marco; S. Spampinato; A. Bedini;
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/68121
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