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Comparison of cyclic δ-opioid peptides with non-peptide δ-agonist spiroindanyloxymorphone (SIOM) using the message-address concept: A molecular modeling study

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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.

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  1. Peng Gao

    Present address: Research Biochemicals International, One Strathmore Road, 01760, Natick, MA, U.S.A.

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  1. Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., 55455, Minneapolis, MN, U.S.A.

    Peng Gao

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Gao, P. Comparison of cyclic δ-opioid peptides with non-peptide δ-agonist spiroindanyloxymorphone (SIOM) using the message-address concept: A molecular modeling study. J Computer-Aided Mol Des 10, 327–336 (1996). https://doi.org/10.1007/BF00124502

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  • DOI: https://doi.org/10.1007/BF00124502

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