ISSN:
1573-4951
Keywords:
δ-Opioid receptor
;
Two-state binding models
;
Molecular template
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Summary Based upon the message-address concept, this molecular modeling study used the δ-selective agonist spiroindanyloxymorphone (SIOM) as a molecular template for a conformational search and analysis of δ-selective opioid peptides. It was assumed that the tyramine moiety plays the same role for δ-opioid receptor recognition in both peptide and non-peptide ligands. Using 20 reported low-energy conformations of Tyr-cyclo[d-Cys-d-Pen]-OH (JOM-13) for comparison, the geometrical relationship of the two aromatic rings present in SIOM was used for the identification of potential active conformations of JOM-13, from which two δ-receptor-binding models (I and II) were constructed. Models I and II differ from each other in the arrangement of the peptide backbones. To evaluate the two models, a conformational search of two other known δ-selective ligands, [d-Pen2,d-Pen5]enkephalin (DPDPE) and [d-Pen2,l-Pen5]enkephalin (DPLPE) was performed, using the geometrical relationship of the two aromatic rings defined in the two receptor-binding models as a molecular template. Among the conformations generated from the molecular simulation, low-energy conformers of DPDPE and DPLPE conforming to models I and II were identified. Unlike model I, conformers of DPDPE and DPLPE that fit model II contain a cis amide bond in the Gly3 residue.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00124502
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