6-N,N-dimethylamino-2,3-naphthalimide: a new environment-sensitive fluorescent probe in delta- and mu-selective opioid peptides

J Med Chem. 2006 Jun 15;49(12):3653-8. doi: 10.1021/jm060343t.

Abstract

A new environment-sensitive fluorophore, 6-N,N-(dimethylamino)-2,3-naphthalimide (6DMN) was introduced in the delta-selective opioid peptide agonist H-Dmt-Tic-Glu-NH(2) and in the mu-selective opioid peptide agonist endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH(2)). Environment-sensitive fluorophores are a special class of chromophores that generally exhibit a low quantum yield in aqueous solution but become highly fluorescent in nonpolar solvents or when bound to hydrophobic sites in proteins or membranes. New fluorescent delta-selective irreversible antagonists (H-Dmt-Tic-Glu-NH-(CH(2))(5)-CO-Dap(6DMN)-NH(2) (1) and H-Dmt-Tic-Glu-Dap(6DMN)-NH(2) (2)) were identified as potential fluorescent probes showing good properties for use in studies of distribution and internalization of delta receptors by confocal laser scanning microscopy.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Line, Tumor
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology
  • Guinea Pigs
  • Imides / chemistry*
  • In Vitro Techniques
  • Male
  • Mice
  • Muscle Contraction
  • Naphthalenes / chemistry*
  • Naphthalimides
  • Neuroblastoma
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / physiology
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Opioid Peptides / chemical synthesis*
  • Opioid Peptides / chemistry
  • Opioid Peptides / pharmacology
  • Radioligand Assay
  • Receptors, Opioid, delta / agonists*
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / metabolism
  • Structure-Activity Relationship

Substances

  • 2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-glutamamide
  • 6-N,N-dimethylamino-2,3-naphthalimide
  • Fluorescent Dyes
  • Imides
  • Naphthalenes
  • Naphthalimides
  • Oligopeptides
  • Opioid Peptides
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • endomorphin 2