Searching for improved mimetic peptides inhibitors preventing conformational transition of amyloid-β 42 monomer

SZÖGI, TITANILLA; BARRERA, EXEQUIEL E.; DELPICCOLO, CARINA M.L.; BROERSEN, KERENSA; GERA, JÁNOS; FÜLÖP, LIVIA; MÉNDEZ, LUCIANA; BOZSÓ, ZSOLT; CIOFFI, FEDERICA; RODRIGUEZ, ANA M.; ENRIZ, RICARDO D.; MATA, ERNESTO G.; PARAGI, GABOR; SZÖGI, TITANILLA; BARRERA, EXEQUIEL E.; DELPICCOLO, CARINA M.L.; BROERSEN, KERENSA; GERA, JÁNOS; FÜLÖP, LIVIA; MÉNDEZ, LUCIANA; CIOFFI, FEDERICA; ENRIZ, RICARDO D.; BOZSÓ, ZSOLT; RODRIGUEZ, ANA M.; MATA, ERNESTO G.; PARAGI, GABOR

BIOORGANIC CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2018 vol. 81 p. 211 - 221

0045-2068

A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ 42 aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ 42 aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotoxicity exerted by Aβ 42 aggregates. The early stage interaction between compound 7 and the Aβ 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 Aβ 42 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.