Structure-activity relationships of the d-opioid-selective agonist deltorphin

MELCHIORRI P; NEGRI L; FALCONIERI-ERSPAMER G; SEVERINI C; CORSI R; 9.GUTIÉRREZ S, DE PAUL AL, PETITO JP, SOSA L, PALMIERI C, SOAJE M, ORGNERO EM, TORRES A.; ERSPAMER V; BARRA D

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 1991 vol. 196 p. 201 - 207

0014-2999

Deltorphins are naturally occurring peptides with high affinity and selectivity for &opioid receptors_ They share withdermorphin. another p-selective opioid agonist, the same N-terminal tripeptide Tyr-D-Xaa-Phe, where D-Xaa is a D-Ala or aD-Met residue. This common sequence appears to be essential for the best fitting of the peptides to both p- or &opioid sites. Westudied 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 moleculetowards S-opioid sites is expressed in the C-terminal region of these peptides. This addressing domain confers high S-selectivity tothe ligand in the following two ways: (i) increased affinity for S-sites; (ii) decreased affinity for p-sites. The sequence of theC-terminal tripeptide appears to be responsible for the high &affinity of the molecules. Negatively charged side chains inhibitp-binding and enhance S-selectivity.