Highly selective fluorescent analogue of the potent delta-opioid receptor antagonist Dmt-Tic

J Med Chem. 2004 Dec 16;47(26):6541-6. doi: 10.1021/jm040128h.

Abstract

A fluorescent tripeptide probe derived by coupling fluorescein to H-Dmt-Tic-Glu-NH2 was developed to interact with delta-opioid receptors with high affinity (Ki = 0.035 nM) and selectivity (Ki(mu)/Ki(delta) = 4371). It acts as an irreversible delta-opioid receptor antagonist, and binding to NG108-15 cells is blocked by the standard nonpeptidic delta-opioid receptor antagonist naltrindole. This probe should prove useful in the study of the distribution of delta-opioid receptors in tissues and the internalization of opioid peptides during signal transduction.

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / ultrastructure
  • Cell Line
  • Dipeptides / chemistry*
  • Electric Stimulation
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / physiology
  • In Vitro Techniques
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Radioligand Assay
  • Rats
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Tetrahydroisoquinolines / chemistry*
  • Vas Deferens / drug effects
  • Vas Deferens / physiology

Substances

  • 2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  • Dipeptides
  • Fluorescent Dyes
  • Receptors, Opioid, delta
  • Tetrahydroisoquinolines