Gao, N., Huang, Y.P., Chu, T.T., Li, Q.Q., Zhou, B., Chen, Y.X., Zhao, Y.F., Li, Y.M. (2019). TDP-43 specific reduction induced by Di-hydrophobic tags conjugated peptides.  Bioorg. Chem. 84(): 254--259.

FBrf0241377

Research paper

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.