Deltorphins are naturally occurring peptides with high affinity and selectivity for δ-opioid receptors. They share with dermorphin, another μ-selective opioid agonist, the same N-terminal tripeptide Tyr-D-Xaa-Phe, where D-Xaa is a D-Ala or a D-Met residue. This common sequence appears to be essential for the best fitting of the peptides to both μ- or δ-opioid sites. We studied the changes in receptor affinity and selectivity and in biological potency of deltorphins due to shortening of the sequence, C-terminal deamidation or single amino acid substitutions. The results support the view that a code addressing the molecule towards δ-opioid sites is expressed in the C-terminal region of these peptides. This addressing domain confers high δ-selectivity to the ligand in the following two ways: (i) increased affinity for δ-sites; (ii) decreased affinity for μ-sites. The sequence of the C-terminal tripeptide appears to be responsible for the high δ-affinity of the molecules. Negatively charged side chains inhibit μ-binding and enhance δ-selectivity.

Structure-activity relationships of the delta-opioid-selective agonists, deltorphins / Melchiorri, Pietro; Negri, Lucia; Falconieri Erspamer, G; Severini, C; Corsi, R; Soaje, M; Erspamer, V; Barra, Donatella. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - STAMPA. - 195(1991), pp. 201-207. [10.1016/0014-2999(91)90536-Y]

Structure-activity relationships of the delta-opioid-selective agonists, deltorphins.

MELCHIORRI, Pietro;NEGRI, Lucia;BARRA, Donatella
1991

Abstract

Deltorphins are naturally occurring peptides with high affinity and selectivity for δ-opioid receptors. They share with dermorphin, another μ-selective opioid agonist, the same N-terminal tripeptide Tyr-D-Xaa-Phe, where D-Xaa is a D-Ala or a D-Met residue. This common sequence appears to be essential for the best fitting of the peptides to both μ- or δ-opioid sites. We studied the changes in receptor affinity and selectivity and in biological potency of deltorphins due to shortening of the sequence, C-terminal deamidation or single amino acid substitutions. The results support the view that a code addressing the molecule towards δ-opioid sites is expressed in the C-terminal region of these peptides. This addressing domain confers high δ-selectivity to the ligand in the following two ways: (i) increased affinity for δ-sites; (ii) decreased affinity for μ-sites. The sequence of the C-terminal tripeptide appears to be responsible for the high δ-affinity of the molecules. Negatively charged side chains inhibit μ-binding and enhance δ-selectivity.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/463389
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