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

Eur J Pharmacol. 1991 Mar 26;195(2):201-7. doi: 10.1016/0014-2999(91)90536-y.


Deltorphins are naturally occurring peptides with high affinity and selectivity for delta-opioid receptors. They share with dermorphin, another mu-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 mu- or delta-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 delta-opioid sites is expressed in the C-terminal region of these peptides. This addressing domain confers high delta-selectivity to the ligand in the following two ways: (i) increased affinity for delta-sites; (ii) decreased affinity for mu-sites. The sequence of the C-terminal tripeptide appears to be responsible for the high delta-affinity of the molecules. Negatively charged side chains inhibit mu-binding and enhance delta-selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / metabolism
  • In Vitro Techniques
  • Male
  • Mice
  • Molecular Conformation
  • Molecular Sequence Data
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Myenteric Plexus / drug effects
  • Myenteric Plexus / metabolism
  • Oligopeptides / metabolism*
  • Oligopeptides / pharmacology
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / metabolism
  • Rats
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid / pharmacology
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Structure-Activity Relationship
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism


  • Oligopeptides
  • Peptides
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • deltorphin