Key Laboratory of Molecular Cytogenetics and Genetic Breeding of Heilongjiang Province, College of Life Science and Technology, Harbin Normal University, Harbin, 150025, China.
Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, Harbin Normal University, Harbin, 150025, P. R. China.
Angew Chem Int Ed Engl. 2021 Apr 6;60(15):8344-8351. doi: 10.1002/anie.202100297. Epub 2021 Mar 3.
The 10-nuclear heteroatom cluster modified {SbW O } was successfully synthesized and exhibited inhibitory activity (IC =0.29 μM). Based on proteomics analysis, Na Ni Sb W -SbW inhibited ATP production by affecting the expression of 16 related proteins, hindering metabolic functions in vivo and cell proliferation due to reactive oxygen species (ROS) stress. In particular, the low expression of FAD/FMN-binding redox enzymes (relative expression ratio of the experimental group to the control=0.43843) could be attributed to the redox mechanism of Na Ni Sb W -SbW , which was consistent with the effect of polyoxometalates (POMs) and FMN-binding proteins on ATP formation. An electrochemical study showed that Na Ni Sb W -SbW combined with FMN to form Na Ni Sb W -SbW -2FMN complex through a one-electron process of the W atoms. Na Ni Sb W -SbW acted as catalase and glutathione peroxidase to protect the cell from ROS stress, and the inhibition rates were 63.3 % at 1.77 μM of NADPH and 86.06 % at 10.62 μM of 2-hydroxyterephthalic acid. Overall, our results showed that POMs can be specific oxidative/antioxidant regulatory agents.
成功合成了 10 核杂原子簇修饰的 {SbW O }，并表现出抑制活性（IC =0.29 μM）。基于蛋白质组学分析，NaNiSbW-SbW 通过影响 16 种相关蛋白的表达来抑制 ATP 的产生，从而干扰体内的代谢功能和细胞增殖，这是由于活性氧（ROS）应激所致。特别是，FAD/FMN 结合氧化还原酶的低表达（实验组与对照组的相对表达比值=0.43843）可能归因于 NaNiSbW-SbW 的氧化还原机制，这与多金属氧酸盐（POMs）和 FMN 结合蛋白对 ATP 形成的影响一致。电化学研究表明，NaNiSbW-SbW 通过 W 原子的单电子过程与 FMN 结合形成 NaNiSbW-SbW-2FMN 复合物。NaNiSbW-SbW 作为过氧化氢酶和谷胱甘肽过氧化物酶，保护细胞免受 ROS 应激，在 1.77 μM 的 NADPH 和 10.62 μM 的 2-羟基对苯二甲酸时，抑制率分别为 63.3%和 86.06%。总体而言，我们的结果表明，POMs 可以作为特异性的氧化/抗氧化调节剂。
