ACS Chemical Biology2022，Vol.17Issue(7) ：9.DOI:10.1021/acschembio.1c00961

Discovery of a Redox-Activatable Chemical Probe for Detection of Cyclooxygenase-2 in Cells and Animals

Uddin, Md. Jashim Lo, Justin Han-Je Oltman, Connor G. Crews, Brenda C. Huda, Tamanna Liu, Justin Kingsley, Philip J. Lin, Shuyang Milad, Mathew Aleem, Ansari M. Asaduzzaman, Abu McIntyre, J. Oliver Duvall, Craig L. Marnett, Lawrence J.
ACS Chemical Biology2022，Vol.17Issue(7) ：9.DOI:10.1021/acschembio.1c00961
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  • NSTL
  • Amer Chemical Soc

Discovery of a Redox-Activatable Chemical Probe for Detection of Cyclooxygenase-2 in Cells and Animals

Uddin, Md. Jashim 1Lo, Justin Han-Je 1Oltman, Connor G. 1Crews, Brenda C. 1Huda, Tamanna 1Liu, Justin 1Kingsley, Philip J. 1Lin, Shuyang 1Milad, Mathew 1Aleem, Ansari M. 1Asaduzzaman, Abu 2McIntyre, J. Oliver 1Duvall, Craig L. 1Marnett, Lawrence J.1
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作者信息

  • 1. Vanderbilt Univ
  • 2. Wichita State Univ
  • 折叠

Abstract

Cyclooxygenase-2 (COX-2) expression is up -regulated in inflammatory tissues and many premalignant and malignant tumors. Assessment of COX-2 protein in vivo, therefore, promises to be a powerful strategy to distinguish pathologic cells from normal cells in a complex disease setting. Herein, we report the first redox-activatable COX-2 probe, fluorocoxib Q (FQ), for in vivo molecular imaging of pathogenesis. FQ inhibits COX-2 selectively in purified enzyme and cell-based assays. FQ exhibits extremely low fluorescence and displays time-and concentration-dependent fluorescence enhancement upon exposure to a redox environment. FQ enters the cells freely and binds to the COX-2 enzyme. FQ exhibits high circulation half-life and metabolic stability sufficient for target site accumulation and demonstrates COX-2-targeted uptake and retention in cancer cells and pathologic tissues. Once taken up, it undergoes redox-mediated transformation into a fluorescent compound fluorocoxib Q-H that results in high signal-to-noise contrast and differentiates pathologic tissues from non-pathologic tissues for real-time in vivo imaging.

Key words

PROSTAGLANDIN SYNTHASE/DIAGNOSTIC METHOD/FATTY-ACIDS/EXPRESSION/COX-2/INFLAMMATION/CANCER/FLUOROCOXIB/GENE/VISUALIZATION

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出版年

2022
ACS Chemical Biology

ACS Chemical Biology

SCI
ISSN：1554-8929
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