| 一种解聚金属-Aβ聚集体的硫磺素T类荧光螯合剂 | |
| A Thioflavin T-Based Fluorescent Chelator Disaggregated Metal-Aβ Aggregates | |
| 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 | |
| 基金项目: 国家自然科学基金(No.21302059,21271079,21072074)和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. | |
| Keywords: Aβ aggregates thioflavin T fluorescent chelators disaggregation | |
| 投稿时间：2014-10-31 修订日期：2015-05-05 | |
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| 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. | |
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