Synthesis and structure-activity relationships of deltorphin analogues.
In order to study the structure-activity relationships of natural opioid deltorphins (H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 and H-Tyr-D-Ala-Phe-Asp [or Glu]-Val-Val-Gly-NH2), 15 analogues were synthesized by the solution method. Their activities were determined in binding studies based on displacement of mu- and delta-receptor selective radiolabels from rat brain membranes and in two bioassays, using guinea pig ileum and mouse vas deferens. The obtained data indicate that the high delta-selectivity of deltorphins can be due to the constitution/conformation of the C-terminal part and, at least in part, to preselection by charge.
Salvadori
S
S
Department of Pharmaceutical Sciences, University of Ferrara, Italy.
Marastoni
M
M
Balboni
G
G
Borea
P A
PA
Morari
M
M
Tomatis
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D011957:Receptors, Opioid; C059567:deltorphin; C060208:deltorphin I, Ala(2)-; C060209:deltorphin II, Ala(2)-