Searching for improved mimetic peptides inhibitors preventing conformational transition of amyloid-β42 monomer
A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ42 aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ42 aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotox...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2018
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| Sorozat: | BIOORGANIC CHEMISTRY
81 |
| doi: | 10.1016/j.bioorg.2018.08.018 |
| mtmt: | 3405755 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/14901 |
| Tartalmi kivonat: | A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ42 aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ42 aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotoxicity exerted by Aβ42 aggregates. The early stage interaction between compound 7 and the Aβ42 monomer was investigated by replica exchange molecular dynamics (REMD) simulations and docking studies. Our theoretical results revealed that compound 7 can elongate the helical conformation state of an early stage Aβ42 monomer and it helps preventing the formation of β-sheet structures by interacting with key residues in the central hydrophobic cluster (CHC). This strategy where early “on-pathway” events are monitored by small molecules will help the development of new therapeutic strategies for Alzheimer’s disease. |
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| Terjedelem/Fizikai jellemzők: | 211-221 |
| ISSN: | 0045-2068 |