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

János Gera, Titanilla Szögi, Zsolt Bozsó, Livia Fülöp, Exequiel E. Barrera, Ana M. Rodriguez, Luciana Méndez, Carina M.L. Delpiccolo, Ernesto G. Mata, Federica Cioffi, Kerensa Broersen, Gabor Paragi, Ricardo D. Enriz* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalBioorganic Chemistry
Publication statusPublished - 1 Dec 2018


  • Alzheimer's disease
  • Amyloid β-peptide
  • Aβ aggregation
  • Mimetic peptides
  • Molecular docking
  • Molecular dynamics


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