TDP-43 specific reduction induced by Di-hydrophobic tags conjugated peptides
TDP-43 specific reduction induced by Di-hydrophobic tags conjugated peptides
复制标题
双疏水标签缀合肽诱导 TDP-43 特异性还原
DOI：
10.1016/j.bioorg.2018.11.042
复制
发表时间：
2019-03-01
影响因子：
5.1
通讯作者：
Li, Yan-Mei
中科院分区：
文献类型：
--
作者：
Gao, Na;Huang, Yun-Peng;Li, Yan-Mei
TAR DNA结合蛋白43（TDP-43）是肌萎缩侧索硬化症（ALS）治疗的关键靶点。本文基于疏水标签策略，设计并合成了一系列单疏水标签或双疏水标签标记的多肽D1-D8。其中，发现D4在细胞中显示出最强的诱导TDP-43降解的能力。D4可降低TDP-43的细胞毒性。此外，D4可以降低转基因果蝇模型中TDP-43的水平。
TAR DNA binding protein 43 (TDP-43) is a key target in amyotrophic lateral sclerosis (ALS) treatment. Here, based on hydrophobic tagging strategy, we designed and synthesized a series of single or double hydrophobic tags conjugated peptides D1-D8. Among them, it was found that D4 displayed strongest ability to induce TDP-43 degradation in cells. D4 could reduce TDP-43 induced cytotoxicity. Besides, D4 could reduce TDP-43 levels in a transgenic drosophila model.