Discovery of Environment-Sensitive Fluorescent Agonists for α 1 -Adrenergic Receptors.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, American Chemical Society.
    • Subject Terms:
      Adrenergic alpha-1 Receptor Agonists/*chemistry ; Adrenergic alpha-1 Receptor Agonists/*pharmacology ; High-Throughput Screening Assays/*methods ; Receptors, Adrenergic, alpha-1/*metabolism; Adrenergic alpha-1 Receptor Agonists/metabolism ; Binding, Competitive ; Calcium/metabolism ; Fluorescence ; Fluorescence Polarization ; Fluorescent Dyes/chemistry ; HEK293 Cells ; Humans ; Luminescence ; Molecular Imaging/methods ; Nitro Compounds/chemistry ; Oxadiazoles/chemistry ; Phenylephrine/chemistry
    • Abstract:
      A series of novel fluorescent agonists were well developed herein with turn-on switch for α 1 -adrenergic receptors (α 1 -ARs) by conjugating the environment-sensitive fluorophore 4-chloro-7-nitrobenzoxadiazole with phenylephrine. Overall, these probes exhibited efficient binding and apparent fluorescence intensity changes (up to 10-fold) upon binding with α 1 -ARs. Moreover, these probes have been successfully applied for selectively imaging α 1 -ARs in the living cells. The dynamic process of α 1 -ARs internalization was traced successfully with these newly designed fluorescent agonists. Fluorescence polarization assay demonstrated specific interactions between these probes and α 1 -ARs. With these new probes, a bioluminescence resonance energy transfer binding assay has been well established and applied to the high-throughput screening of unlabeled α 1 -ARs agonist and antagonist. It is expected that these environment-sensitive fluorescent turn-on agonists may provide useful new tools in studying pharmacology and physiology of α 1 -ARs during drug discovery.
    • Accession Number:
      0 (4-chloro-7-nitro-1,2,3-benzoxadiazole)
      0 (Adrenergic alpha-1 Receptor Agonists)
      0 (Fluorescent Dyes)
      0 (Nitro Compounds)
      0 (Oxadiazoles)
      0 (Receptors, Adrenergic, alpha-1)
      1WS297W6MV (Phenylephrine)
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 20190720 Date Completed: 20201118 Latest Revision: 20201118
    • Publication Date:
      20231215
    • Accession Number:
      10.1021/acs.analchem.9b01059
    • Accession Number:
      31321979