Yuan Mingliang, Ma Xiaojie, Jiang Tianyu, Gao Yuqi, Cui Yuanyuan, Zhang Chaochao, Yang Xingye, Huang Yun, Du Lupei, Yampolsky Ilia, Li Minyong
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
Department of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
Org Biomol Chem. 2017 Dec 13;15(48):10238-10244. doi: 10.1039/c7ob01656e.
The prodrug or caged-luciferin strategy affords an excellent platform for persistent bioluminescence imaging. In the current work, we designed and synthesized ten novel pro-substrates for Renilla luciferase by introducing ester protecting groups of different sizes into the carbonyl group of the free luciferin 1. Taking advantage of intracellular esterases, lipases, and nucleophilic substances, the ester protecting groups were hydrolyzed, resulting in the release of a free luciferin and a bioluminescence signal turn-on. Among the tested pro-substrates, the butyryloxymethyl luciferin 7 exhibited low cytotoxicity and a prolonged luminescence signal both in cellulo and in vivo. Therefore, the butyryloxymethyl luciferin 7 can act as a promising substrate for noninvasive extended imaging in diagnostic and therapeutic fields.
前药或笼状荧光素策略为持续生物发光成像提供了一个出色的平台。在当前工作中，我们通过将不同大小的酯保护基团引入游离荧光素1的羰基，设计并合成了十种用于海肾荧光素酶的新型前体底物。利用细胞内酯酶、脂肪酶和亲核物质，酯保护基团被水解，导致游离荧光素的释放和生物发光信号的开启。在所测试的前体底物中，丁酰氧基甲基荧光素7在细胞内和体内均表现出低细胞毒性和延长的发光信号。因此，丁酰氧基甲基荧光素7可作为诊断和治疗领域中非侵入性延长成像的有前景的底物。
