Selective opioid dipeptides

Biochem Biophys Res Commun. 1994 Feb 15;198(3):933-9. doi: 10.1006/bbrc.1994.1133.

Abstract

The surprising change of selectivity induced by the change of chirality in peptides containing the tetrahydro-3-isoquinoline carboxylic acid (Tic) in second position, interpreted as a conformational preference induced on the Tyr-Xaa-Phe domain, can instead be attributed to the Tyr-Tic message domain. The relative spatial disposition of the aromatic ring of delta-selective non peptidic opiates is compatible with a message domain, in opioid peptides, of only two residues. This hypothesis was tested through the synthesis of Tyr-L-Tic-NH2, Tyr-D-Tic-NH2, Tyr-L-Tic-Ala-NH2, Tyr-L-Tic-Ala-OH and Tyr-D-Tic-Ala-NH2. Peptides containing Tyr-L-Tic- behave as very selective delta antagonists and those containing Tyr-DTic- as non selective agonists. This is the first case of opioid peptides containing a two-residue message domain and of opioid dipeptides with substantial opioid activity.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • Brain / metabolism
  • Cell Membrane / metabolism
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry*
  • Dipeptides / pharmacology
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / metabolism
  • Enkephalins / pharmacology
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / physiology
  • In Vitro Techniques
  • Isoquinolines*
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Narcotics / chemical synthesis
  • Narcotics / chemistry*
  • Narcotics / pharmacology
  • Oligopeptides / pharmacology
  • Protein Conformation
  • Radioligand Assay
  • Rats
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Synaptosomes / metabolism
  • Tetrahydroisoquinolines*

Substances

  • Dipeptides
  • Enkephalins
  • Isoquinolines
  • Narcotics
  • Oligopeptides
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Tetrahydroisoquinolines
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • deltorphin I, Ala(2)-
  • 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  • Enkephalin, D-Penicillamine (2,5)-