6-N,N-Dimethylamino-2,3-Naphthalimide a New Environment-Sensitive Fluorescent Probe in delta-Selective and mu-Selective Opioid Peptides

A new environment-sensitive fluorophore, 6-N,N-dimethylamino-2,3-naphthalimide (6DMN) was introduced in the ?-selective opioid agonist H-Dmt-Tic-Glu-NH2 and in the ?-selective opioid agonist endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2). 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 ?-selective irreversible antagonists [H-Dmt-Tic-Glu-NH-(CH2)5-CO-Dap(6DMN)-NH2(1) and H-Dmt-Tic-Glu-Dap(6DMN)-NH2)] (2) were identified as potential fluorescent probes showing properties suitable for studies of distribution and internalization of ?-opioid receptors by confocal laser scanning microscopy.