Deltorphins: A Family of Naturally Occurring Peptides With High Affinity and Selectivity for Delta Opioid Binding Sites

Proc Natl Acad Sci U S A. 1989 Jul;86(13):5188-92. doi: 10.1073/pnas.86.13.5188.

Abstract

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid binding sites than any other natural compound known. Two deltorphins with the sequence Tyr-Ala-Phe-Asp(or Glu)-Val-Val-Gly-NH2 have been isolated from skin extracts of Phyllomedusa bicolor. The alanine in position 2 is in the D configuration. These peptides, [D-Ala2]deltorphins I and II, show an even higher affinity for delta receptors than the previously characterized deltorphin, which contains D-methionine as the second amino acid. These peptides show some similarity to another constituent of Phyllomedusa skin, dermorphin, which is highly selective for mu-opioid receptors. These peptides all have the N-terminal sequence Tyr-D-Xaa-Phe, where D-Xaa is either D-alanine or D-methionine. While this structure seems to be capable of activating both mu and delta opioid receptors, differences in the C-terminal regions of these peptides are probably responsible for the observed high receptor selectivity of dermorphin and deltorphin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anura
  • Brain / metabolism*
  • Enkephalins / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Kinetics
  • Male
  • Membranes / metabolism
  • Molecular Sequence Data
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Oligopeptides / isolation & purification*
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacology
  • Rats
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, delta
  • Skin
  • Vas Deferens / drug effects
  • Vas Deferens / physiology

Substances

  • Enkephalins
  • Oligopeptides
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • deltorphin I, Ala(2)-
  • deltorphin II, Ala(2)-