Searching for improved mimetic peptides inhibitors preventing conformational transition of amyloid-β42 monomer

Gera, János; Szögi, Titanilla [Szögi, Titanilla (Neurobiológia), szerző]; Bozsó, Zsolt [Bozsó, Zsolt (Peptid kémia), szerző]; Fülöp, Livia [Fülöp, Lívia (Neurodegeneratív ...), szerző]; Barrera, Exequiel E; Rodriguez, Ana M; Méndez, Luciana; Delpiccolo, Carina ML; Mata, Ernesto G; Cioffi, Federica; Broersen, Kerensa; Paragi, Gabor [Paragi, Gábor (molekulafizika, m...), szerző] MTA-SZTE Biomimetikus Rendszerek Kutatócsoport (SZTE / ÁOK / OVI); Enriz, Ricardo D

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
Megjelent: BIOORGANIC CHEMISTRY 0045-2068 1090-2120 81 pp. 211-221 2018
  • SJR Scopus - Drug Discovery: Q2
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.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSL
2019-11-22 19:20