An Activatable Chemiluminescent Probe for Sensitive Detection of γ-Glutamyl Transpeptidase Activity in Vivo,Analytical Chemistry

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An Activatable Chemiluminescent Probe for Sensitive Detection of γ-Glutamyl Transpeptidase Activity in Vivo
Analytical Chemistry ( IF 6.7 ) Pub Date : 2019-10-07 , DOI: 10.1021/acs.analchem.9b02839
Ruibing An ₁ , Shixuan Wei ₁ , Zheng Huang ₁ , Fei Liu ₁ , Deju Ye ₁

Affiliation

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.

中文翻译：

用于体内检测γ-谷氨酰转肽酶活性的可激活化学发光探针

在与目标分子靶标相互作用后显示出增强的化学发光的可活化化学发光探针，由于背景低，灵敏度高和在生物组织中的穿透深度提高，为传感和生物成像提供了有前途的工具。在这里，我们报道了一种γ-谷氨酰转肽酶（GGT）可激活的化学发光探针，用于在体外和活体小鼠中实时检测GGT的活性。该探针是通过将具有GGT识别底物（γ-Glu）和自消灭性连接基（p-氨基苄醇），最初是化学发光的。与GGT相互作用后，可以在水溶液中以超过800倍的打开比率实现强化学发光，从而可以在体外和活细胞中以超高的信号背景比和灵敏度来特异性检测GGT活性。我们证明该探针可可靠地定量血清中的GGT，从而可以准确报告脂多糖治疗的小鼠血清中GGT的水平升高。此外，通过对GGT活性进行实时化学发光成像，设计的探针对于在静脉内全身给药后在活体小鼠中检测GGT阳性肿瘤是可行的。这项研究表明，GGT激活型化学发光探针在血清分析和分子成像中具有很高的潜力，

更新日期：2019-10-07

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