Luciferin Amides Enablein VivoBioluminescence Detection of Endogenous Fatty Acid Amide Hydrolase Activity,Journal of the American Chemical Society

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Luciferin Amides Enablein VivoBioluminescence Detection of Endogenous Fatty Acid Amide Hydrolase Activity
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2015-07-02 , DOI: 10.1021/jacs.5b04357
David M. Mofford ₁ , Spencer T. Adams ₁ , G. S. Kiran Kumar Reddy ₁ , Gadarla Randheer Reddy ₁ , Stephen C. Miller ₁

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Firefly luciferase is homologous to fatty acyl-CoA synthetases. We hypothesized that the firefly luciferase substrate d-luciferin and its analogs are fatty acid mimics that are ideally suited to probe the chemistry of enzymes that release fatty acid products. Here, we synthesized luciferin amides and found that these molecules are hydrolyzed to substrates for firefly luciferase by the enzyme fatty acid amide hydrolase (FAAH). In the presence of luciferase, these molecules enable highly sensitive and selective bioluminescent detection of FAAH activity in vitro, in live cells, and in vivo. The potency and tissue distribution of FAAH inhibitors can be imaged in live mice, and luciferin amides serve as exemplary reagents for greatly improved bioluminescence imaging in FAAH-expressing tissues such as the brain.

中文翻译：

荧光素酰胺能够在体内生物发光检测内源性脂肪酸酰胺水解酶活性

萤火虫萤光素酶与脂肪酰基辅酶A合成酶同源。我们假设萤火虫荧光素酶底物 d-荧光素及其类似物是脂肪酸模拟物，非常适合探测释放脂肪酸产物的酶的化学性质。在这里，我们合成了荧光素酰胺，并发现这些分子被脂肪酸酰胺水解酶 (FAAH) 水解为萤火虫荧光素酶的底物。在荧光素酶存在的情况下，这些分子能够在体外、活细胞和体内对 FAAH 活性进行高度灵敏和选择性的生物发光检测。FAAH 抑制剂的效力和组织分布可以在活小鼠中成像，荧光素酰胺可作为示例性试剂，用于大大改善 FAAH 表达组织（如大脑）中的生物发光成像。

更新日期：2015-07-02

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