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  • Title: An Activatable Chemiluminescent Probe for Sensitive Detection of γ-Glutamyl Transpeptidase Activity in Vivo.
    Author: An R, Wei S, Huang Z, Liu F, Ye D.
    Journal: Anal Chem; 2019 Nov 05; 91(21):13639-13646. PubMed ID: 31560193.
    Abstract:
    Activatable chemiluminescent probes that show enhanced chemiluminescence upon interaction with a molecular target of interest have offered promising tools for sensing and bioimaging in terms of low background, high sensitivity, and improved penetration depth in biological tissues. Here, we reported a γ-glutamyl transpeptidase (GGT) activatable chemiluminescent probe for real-time detection of GGT activity in vitro and in living mice. The probe was designed by caging an electron-withdrawing acrylic group-substituted Schaap's phenoxy-dioxetane with a GGT-recognitive substrate (γ-Glu) and a self-immolative linker (p-aminobenzyl alcohol), which was initially chemiluminescence off. Upon interaction with GGT, strong chemiluminescence with a more than 800-fold turn-on ratio could be achieved in aqueous solution, allowing to specifically detect GGT activity with ultrahigh signal-to-background ratio and sensitivity in vitro and in live cells. We demonstrated that the probe was reliable to quantify the GGT in serum, permitting to accurately report the elevated levels of GGT in lipopolysaccharide-treated mouse serum. Moreover, through real-time chemiluminescence imaging of GGT activity, the designed probe was feasible to detect GGT-positive tumors in living mice after intravenous systemic administration. This study demonstrates the high potential of GGT-activatable chemiluminescent probe for serum assays and molecular imaging, which might find wide applications in diagnosis of GGT-related diseases.
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