钴取代的链状Strandberg结构磷钼酸盐的合成及其对Aβ错误折叠聚集过程的调节
Synthesis of a Linear Cobalt-Substituted Strandberg-Type Polyphospolybdate with Ability in Modulating Conformation of Aβ-Peptide Misfolding Aggregation
作者单位E-mail
滑继爱 太原工业学院化学与化工系, 太原 030008 jiaihua01660@163.com 
卫雪曼 海军军医大学第一附属医院老年病科, 上海 200081  
张娜 太原工业学院生化药学实验室, 太原 030008  
陈鹏举 太原工业学院化学与化工系, 太原 030008  
马翔 太原工业学院生化药学实验室, 太原 030008
南京大学配位化学国家重点实验室, 南京 210023 
maxiang@tit.edu.cn 
摘要: 设计并合成了一例钴取代的Strandberg结构的磷钼酸盐(H2en)6{[Co (H2O)4](P2Mo5O23)}3·11H2O (简称CoPM,en=乙二胺),其结构通过元素分析、红外光谱、热重分析以及X射线单晶衍射进行了表征。结果显示,CoPM是由磷钼氧簇[P2Mo5O23]6-和钴配合物[Co (H2O)4]2+交替连接而形成链状结构,其中每个循环单元包含3个{[Co (H2O)4](P2Mo5O23)}4-结构单位,它们各自的延展方向与配位环境均不相同。利用硫黄素T荧光法、比浊法、圆二色谱、NMR等研究了CoPM对淀粉样蛋白(Aβ)错误折叠过程的干预,发现CoPM能够通过调节β错误构象,从而减少有害聚集体的形成。2',7'-二氯荧光素(DCF)荧光及细胞毒性实验表明CoPM还可以消除由Cu2+-Aβ所产生的活性氧物种(ROS),进而保护PC12细胞及其突触免受Aβ错误折叠聚集体及氧化应激的损害。
关键词: 多聚磷钼酸盐  抗氧化  构象调节  蛋白错误折叠疾病  淀粉样蛋白
基金项目: 山西省“1331”工程、山西省基础研究计划项目(No.201901D211453,20210302124333)、山西省高等学校科技创新项目(No.STIP2020L0644)、配位化学国家重点实验室开放课题项目(No.SKLCC202204)资助
Abstract: A linear Co-substituted Strandberg-type polyphosphomolybdate (H2en)6{[Co(H2O)4] (P2 Mo5O23)}3·11H2O (abbreviated as CoPM, en=ethylenediamine) has been synthesized and structurally characterized by elemental analyses, IR spectrum, thermogravimetric analysis, and single-crystal X-ray diffraction. Structural analysis reveals that the molecular structural unit of CoPM consists of[P2Mo5O23]6- cluster, and Co-complex[Co(H 2O)4]2+, and they join alternately to form the 1D infinite extension skeleton of CoPM. Furthermore, each cyclic unit of the CoPM chain contains three {[Co(H2O)4](P2Mo5O23)}4- units in solid states based on bond valence sums (BVS) calculation. The intervention of CoPM on the misfolding process of amyloid β-protein (Aβ) was studied by the thioflavin T fluorescence method, turbidimetric method, circular dichroism, and NMR. The results indicate that CoPM can modulate the β-sheet-rich conformation of Aβ aggregates, and thus reduce the formation of toxic species. Moreover, 2', 7'-dichlorofluorescein (DCF) fluorescence and cytotoxicity experiments showed that CoPM could also eliminate reactive oxygen species (ROS) produced by Cu2+-Aβ aggregates. It can inhibit the cytotoxicity of β-sheet-rich species and protect synapses of PC12 cells.
Keywords: polyphosphomolybdate  anti-oxidation  conformation modulation  protein-misfolding disease  amyloid β-peptide
投稿时间:2022-03-21 修订日期:2022-08-23
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滑继爱,卫雪曼,张娜,陈鹏举,马翔.钴取代的链状Strandberg结构磷钼酸盐的合成及其对Aβ错误折叠聚集过程的调节[J].无机化学学报,2022,38(10):1908-1918.
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