Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy , Shandong University , Jinan , Shandong 250012 , China.
State Key Laboratory of Microbial Technology , Shandong University , Jinan , Shandong 250100 , China.
Anal Chem. 2018 Aug 7;90(15):9545-9550. doi: 10.1021/acs.analchem.8b02266. Epub 2018 Jul 18.
Pantetheinase, a glycosylphosphatidylinositol (GPI) anchored enzyme, overexpresses in intestine, liver, and kidney with various biological functions such as its linkage to the inflammation and some metabolic diseases. It can hydrolyze pantetheine to cysteamine, an antioxidant, and pantothenic acid (Vitamin B5) that is an essential component of coenzyme A (CoA). Until now, very few analytic methods were developed for this enzyme, hampering the further investigation of its biological functions. In this work, we report the design, synthesis, and biological examination of a highly sensitive bioluminogenic probe for pantetheinase with a limit of detection of 1.14 ng/mL. Furthermore, animal experiments validated that our probe can be applied to detect the endogenous pantetheinase activity. To the best of our knowledge, this is the first bioluminogenic probe achieving the detection of pantetheinase level in vivo.
酰基载体蛋白水解酶是一种糖基磷脂酰肌醇（GPI）锚定酶，在肠道、肝脏和肾脏中过度表达，具有多种生物学功能，如与炎症和一些代谢性疾病有关。它可以将泛肽水解为半胱胺，一种抗氧化剂，以及泛酸（维生素 B5），这是辅酶 A（CoA）的必需组成部分。到目前为止，针对这种酶的分析方法非常少，这阻碍了对其生物学功能的进一步研究。在这项工作中，我们报告了一种用于酰基载体蛋白水解酶的高灵敏度生物发光探针的设计、合成和生物学检测，其检测限为 1.14ng/mL。此外，动物实验验证了我们的探针可用于检测内源性酰基载体蛋白水解酶的活性。据我们所知，这是第一个能够在体内检测酰基载体蛋白水解酶水平的生物发光探针。
