Near-Infrared Photoactivatable Oxygenation Catalysts of Amyloid Peptide
Near-Infrared Photoactivatable Oxygenation Catalysts of Amyloid Peptide
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DOI：
10.1016/j.chempr.2018.02.008
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发表时间：
2018-04-12
期刊：
影响因子：
23.5
通讯作者：
Kanai, Motomu
中科院分区：
文献类型：
--
作者：
Ni, Jizhi;Taniguchi, Atsuhiko;Kanai, Motomu
淀粉样肽和蛋白的毒性聚集与包括阿尔茨海默病（AD）在内的许多人类疾病密切相关。在这里，我们开发了生物相容的光氧合催化剂9，它可以选择性地阻止和降解AD相关的淀粉样β肽（A β）的致病性聚集在近红外（NIR）光照射。基于荧光A β探针CRANAD-2的结构，引入溴原子以增加用于光氧化的单线态氧的产生。使用久洛尼定和全氟烷基硼酸酯部分作为电子供体和受体组件，分别显着增强的光催化活性和降低的光毒性。在细胞存在下，在NIR照射下，聚集的A β的光氧化作用减弱了A β的细胞毒性。NIR的组织渗透性使得聚集的A β在小鼠皮肤下能够催化光氧化。此外，将催化剂注射到AD模型小鼠脑沿着NIR光照射导致脑中完整A β水平显著降低。
Toxic aggregation of amyloid peptide and protein is intimately related to a number of human diseases, including Alzheimer's disease (AD). Here, we developed biocompatible photooxygenation catalyst 9, which can selectively oxygenate and degrade the pathogenic aggregation of AD-related amyloid-beta peptide (A beta) under near-infrared (NIR) light irradiation. On the basis of the structure of a fluorescent A beta probe, CRANAD-2, a bromine atom was introduced to increase the production of singlet oxygen for photooxygenation. The use of julolidine and perfluoroalkylborate moieties as electron-donor and -acceptor components, respectively, markedly enhanced the photocatalytic activity and reduced phototoxicity. Photooxygenation of aggregated A beta by 9 under NIR irradiation in the presence of cells attenuated the cytotoxicity of A beta. The tissue permeability of NIR enabled catalytic photooxygenation of aggregated A beta under the mouse skin. Moreover, injection of the catalyst to the AD-model mouse brain along with NIR light irradiation led to a significant decrease in the intact A beta level in the brain.