| Autor: |
Jinxia Lu, Qin Cao, Chuchu Wang, Jing Zheng, Feng Luo, Jingfei Xie, Yichen Li, Xiaojuan Ma, Lin He, David Eisenberg, James Nowick, Lin Jiang, Dan Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Frontiers in Molecular Neuroscience, Vol 12 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1662-5099 |
| DOI: |
10.3389/fnmol.2019.00054 |
| Popis: |
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 β (Aβ) 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 β-strand conformation, which significantly improves the potency of the inhibitors against Aβ aggregation and toxicity. Furthermore, we show that by targeting different Aβ segments, the designed peptide inhibitors can selectively recognize different species of Aβ. 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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