Fine-tuning thio-pyridazinediones as SMDC scaffolds (with intracellular thiol release via a novel self-immolative linker)
Fine-tuning thio-pyridazinediones as SMDC scaffolds (with intracellular thiol release via a novel self-immolative linker)
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DOI：
10.1039/c9cc08744c
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发表时间：
2020-01-21
影响因子：
4.9
通讯作者：
Chudasama, Vijay
中科院分区：
文献类型：
--
作者：
Fernandez, Marcos;Shamsabadi, Andre;Chudasama, Vijay
在此，我们报告了硫代烷基-和硫代芳基-哒嗪二酮类化合物库的合成，用于基于硫醇的货物自分解释放。双硫代芳基-哒嗪二酮显示对血清蛋白白蛋白稳定，但在细胞内条件下不稳定。衍生的类似物在细胞硫醇条件下发生自降解，如通过LC-MS/释放开启荧光的荧光团所证明的;硫醇-哒嗪二酮的多功能性通过在相同中心分子上含有三个不同官能团的SMDC前体的合成来证明。
Herein we report the synthesis of a library of thioalkyl- and thioaryl-pyridazinediones for thiol-based self-immolative release of cargo. A bisthioaryl-pyridazinedione is shown to be stable to serum protein albumin but unstable in intracellular conditions. A derivatised analogue underwent self-immolative degradation in cellular thiol conditions as evidenced by LC-MS/release of a turn-on fluorescence fluorophore; versatility of the thiol-pyridazinedione is demonstrated through synthesis of SMDC precursors that contain three different functional groups on the same central molecule.