6-N,N-Dimethylamino-2,3-naphthalimide:  A New Environment-Sensitive Fluorescent Probe in δ- and μ-Selective Opioid Peptides

• Published in: Journal of medicinal chemistry Vol. 49; no. 12; pp. 3653 - 3658
• Main Authors: Vázquez, M. Eugenio, Blanco, Juan B, Salvadori, Severo, Trapella, Claudio, Argazzi, Roberto, Bryant, Sharon D, Jinsmaa, Yunden, Lazarus, Lawrence H, Negri, Lucia, Giannini, Elisa, Lattanzi, Roberta, Colucci, Mariantonella, Balboni, Gianfranco
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.06.2006; Amer Chemical Soc
• Subjects: Animals; Binding, Competitive; Biological and medical sciences; Cell Line, Tumor; Cell receptors; Cell structures and functions; Chemistry, Medicinal; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacology; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Imides - chemistry; In Vitro Techniques; Life Sciences & Biomedicine; Male; Medical sciences; Mice; Miscellaneous; Molecular and cellular biology; 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; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Radioligand Assay; Receptors, Opioid, delta - agonists; Receptors, Opioid, delta - metabolism; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - metabolism; Science & Technology; Structure-Activity Relationship; AMINO-ACID; POTENT; ANALOGS; OPIATE RECEPTOR; HIGH-AFFINITY; ANTAGONISM; AGONISTS; BINDING; DMT-TIC PHARMACOPHORE; LIVING CELLS; Peptides; Rodentia; Tripeptide; Confocal microscopy; Selectivity; Neuroblastoma; δ Opioid receptor; In vitro; Opioid peptide; Fluorescence spectrometry; Imide; Vertebrata; Scanning microscope; Mammalia; Analysis method; Mouse; Animal; Fluorescent compound; Confocal laser scanning microscopy
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm060343t

A new environment-sensitive fluorophore, 6-N,N-(dimethylamino)-2,3-naphthalimide (6DMN) was introduced in the δ-selective opioid peptide agonist H-Dmt-Tic-Glu-NH2 and in the μ-selective opioid peptide 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 δ-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 good properties for use in studies of distribution and internalization of δ receptors by confocal laser scanning microscopy.