一种解聚金属-Aβ聚集体的硫磺素T类荧光螯合剂

引用本文: 张勇, 张哲, 董雄伟, 尹文星, 章丹, 刘长林. 一种解聚金属-Aβ聚集体的硫磺素T类荧光螯合剂[J]. 无机化学学报, 2015, 31(8): 1495-1504. doi: 10.11862/CJIC.2015.233 shu

Citation: ZHANG Yong, ZHANG Zhe, DONG Xiong-Wei, YIN Wen-Xing, ZHANG Dan, LIU Chang-Lin. A Thioflavin T-Based Fluorescent Chelator Disaggregated Metal-Aβ Aggregates[J]. Chinese Journal of Inorganic Chemistry, 2015, 31(8): 1495-1504. doi: 10.11862/CJIC.2015.233 shu

一种解聚金属-Aβ聚集体的硫磺素T类荧光螯合剂

张勇 ^1,2, ,
张哲 ^1, ,
董雄伟 ^1, ,
尹文星 ^1, ,
章丹 ^1, ,
刘长林 ^{1,
,}

1.
1. 华中师范大学化学学院, 武汉 430079;
2.
2. 湖北理工学院化学与化工学院, 黄石 435003

通讯作者: 刘长林,E-mail:liuchl@mail.ccnu.edu.cn

基金项目:
国家自然科学基金(No.21302059,21271079,21072074) (No.21302059,21271079,21072074)

湖北省教育厅青年人才(No.Q20134402)资助项目。 (No.Q20134402)

摘要: 以硫磺素T为母体,合成和表征了一种解聚金属-Aβ聚集体的荧光螯合剂5-氨基-2-(苯并[d]噻唑-2-基)苯酚(FC-9),研究了它与金属-Aβ聚集体的相互作用以及由此导致的Aβ聚集体的构象、形貌和毒性变化。结果表明,FC-9不仅能识别各种Aβ40/Aβ42聚集体,而且还能使金属-Aβ40/42聚集体解聚。FC-9与金属-Aβ聚集体相互作用后,聚集体的形貌由纤维状转化为无定形状,其β-折叠构象也减少了。FC-9还能够跨过细胞膜,符合严格的Lipinski类药标准,在一定程度上可抑制由Cu-Aβ40聚集体产生的毒性,这使得FC-9在螯合治疗老年痴呆症方面可能具有潜在的应用前景。

关键词:

Aβ聚集体;硫磺素T;荧光螯合剂;解聚

English

A Thioflavin T-Based Fluorescent Chelator Disaggregated Metal-Aβ Aggregates

1.
1. College of Chemistry, Central China Normal University, Wuhan 430079, China;
2.
2. College of Chemistry and Chemical Engineering, Hubei Polytechnic University, Huangshi, Hubei 435003, China

Corresponding author: 刘长林,E-mail:liuchl@mail.ccnu.edu.cn

Received Date: 31 October 2014
Fund Project:
国家自然科学基金(No.21302059,21271079,21072074)

湖北省教育厅青年人才(No.Q20134402)资助项目。

Abstract: A thioflavin T-based fluorescent chelator 5-amino-2-(benzo[d]thiazol-2-yl)phenol (FC-9) was synthesized and characterized. Its interaction with metal-Aβ aggregates and the change of morphology, conformation, cytotoxicity of the resulting Aβ aggregates were investigated. The results showed that FC-9 can not only recognize different Aβ40/Aβ42 aggregates but also disaggregate metal-Aβ40/Aβ42 aggregates. After the interaction between FC-9 and metal-Aβ40/Aβ42 aggregates, the morphology of aggregates changed from fibril to amorphousness, and their β-sheet conformation was also reduced. Moreover, the cell membrane penetration of FC-9 fulfilled common drug-like criteria, and it can inhibit cytotoxicity of the Cu-Aβ40 aggregates, indicating that it could have potential prospect in the treatment of Alzheimer disease. CCDC: 960540.

Key words:

Aβ aggregates;thioflavin T;fluorescent chelators;disaggregation

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一种解聚金属-Aβ聚集体的硫磺素T类荧光螯合剂

通讯作者: 刘长林,E-mail:liuchl@mail.ccnu.edu.cn

English

A Thioflavin T-Based Fluorescent Chelator Disaggregated Metal-Aβ Aggregates

Corresponding author: 刘长林,E-mail:liuchl@mail.ccnu.edu.cn

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

一种解聚金属-Aβ聚集体的硫磺素T类荧光螯合剂

通讯作者: 刘长林,E-mail:liuchl@mail.ccnu.edu.cn

English

A Thioflavin T-Based Fluorescent Chelator Disaggregated Metal-Aβ Aggregates

Corresponding author: 刘长林,E-mail:liuchl@mail.ccnu.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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