Structure-Based Peptide Inhibitor Design of Amyloid-β Aggregation
Structure-Based Peptide Inhibitor Design of Amyloid-β Aggregation
复制标题
基于结构的淀粉样蛋白-β 聚集肽抑制剂设计
DOI：
10.3389/fnmol.2019.00054
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发表时间：
2019-03-04
影响因子：
4.8
通讯作者：
Li, Dan
中科院分区：
文献类型：
--
作者：
Lu, Jinxia;Cao, Qin;Li, Dan
Many human neurodegenerative diseases are associated with amyloid fibril formation. Inhibition of amyloid formation is of importance for therapeutics of the related diseases. However, the development of selective potent amyloid inhibitors remains challenging. Here based on the structures of amyloid beta (A beta) fibrils and their amyloid-forming segments, we designed a series of peptide inhibitors using RosettaDesign. We further utilized a chemical scaffold to constrain the designed peptides into beta-strand conformation, which significantly improves the potency of the inhibitors against A beta aggregation and toxicity. Furthermore, we show that by targeting different A beta segments, the designed peptide inhibitors can selectively recognize different species of A beta. Our study developed an approach that combines the structure-based rational design with chemical modification for the development of amyloid inhibitors, which could be applied to the development of therapeutics for different amyloid-related diseases.
