Relationship between receptor affinity and topography of N-terminally extended and bridged [Tyr1-->Asp4]deltorphin C analogues: novel probes for the delta-opioid receptor.
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.
Department of Pharmaceutical Science, University of Ferrara, Italy.
S
S
Salvadori
S D
SD
Bryant
P A
PA
Temussi
D M
DM
Bundy
M
M
Attila
R
R
Tomatis
L H
LH
Lazarus
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D015195:Drug Design; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism
D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C060208:deltorphin I, Ala(2)-