Relationship between receptor affinity and topography of N-terminally extended and bridged [Tyr1-->Asp4]deltorphin C analogues: novel probes for the delta-opioid receptor

• Published in: European journal of pharmacology Vol. 230; no. 3; p. 357
• Main Authors: Salvadori, S, Bryant, S D, Temussi, P A, Bundy, D M, Attila, M, Tomatis, R, Lazarus, L H
• Format: Journal Article
• Language: English
• Published: Netherlands 19-01-1993
• Subjects: Amino Acid Sequence; Animals; Brain - metabolism; Drug Design; In Vitro Techniques; Models, Molecular; Molecular Sequence Data; Oligopeptides - chemical synthesis; Oligopeptides - metabolism; Protein Conformation; Rats; Receptors, Opioid, delta - metabolism; Structure-Activity Relationship; Synaptosomes - metabolism
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(93)90573-Z

Receptor binding of N-terminally extended Tyr1 deltorphin C analogues diminished delta and mu affinities, but with only a moderate loss in delta selectivity. Pseudopeptide bridged [Tyr1-->Aps4]deltorphin C analogues drastically decreased delta affinity to yield peptides with poor delta selectivity. Low energy conformers of the peptides revealed that the bridge modifies the spatial orientation of the backbone of the N- and C-terminal sequences with respect to deltorphin C. The data indicate that the delta receptor site can accommodate an opioid peptide containing an N-terminal aliphatic extension on amino-Tyr1, but not a heptapeptide conformationally constrained between residues 1 and 4.