Searching for improved mimetic peptides inhibitors preventing conformational transition of amyloid-β 42 monomer
A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotoxicit...
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Veröffentlicht in: | Bioorganic chemistry 2018-12, Vol.81, p.211 |
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Hauptverfasser: | , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
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Zusammenfassung: | A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ
aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ
aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotoxicity exerted by Aβ
aggregates. The early stage interaction between compound 7 and the Aβ
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 Aβ
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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ISSN: | 1090-2120 |
DOI: | 10.1016/j.bioorg.2018.08.018 |