期刊
BIOORGANIC CHEMISTRY
卷 81, 期 -, 页码 211-221出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2018.08.018
关键词
Mimetic peptides; Alzheimer's disease; Amyloid beta-peptide; A beta aggregation; Molecular dynamics; Molecular docking
资金
- Universidad Nacional de San Luis (UNSL)
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 2015-1769]
- CONICET
- ANPCyT
- UNR
- CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina)
- Hungarian government [GINOP-2.3.2-15-2016-00034]
- Hungarian Scientific Research Fund (OTKA) [K111862]
A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of A beta(42) aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated A beta(42) aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotoxicity exerted by A beta(42) aggregates. The early stage interaction between compound 7 and the A beta(42) 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 A beta(42) monomer and it helps preventing the formation of beta-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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