Design and synthesis of new trehalose-conjugated pentapeptides as inhibitors of Aβ(1-42) fibrillogenesis and toxicity

Paolo De Bona, Maria Laura Giuffrida, Filippo Caraci, Agata Copani, Bruno Pignataro, Francesco Attanasio, Sebastiano Cataldo, Giuseppe Pappalardo, Enrico Rizzarelli

Research output: Contribution to journalArticle

Abstract

Aggregation of the amyloid Aβ peptide and its accumulation into insoluble deposits (plaques) are believed to be the main cause of neuronal dysfunction associated with Alzheimer's disease (AD); small molecules that can interfere with the Aβ amyloid fibril formation are therefore of interest for a potential therapeutic strategy. Three new trehalose-conjugated peptides of the well known β-sheet breaker peptide iAβ5p,were synthesized. The disaccharide was covalently attached to different sites of the LPFFD peptide chain, i.e. at the N-terminus, C-terminus or at the Asp side chain. CD spectroscopy in different solvents was used to assess changes in the peptide conformation of these compounds. The effects of these glycopeptides on the self-assembly and morphology of Aβ aggregates were investigated by ThT fluorescence assay and dynamic Scanning Force Microscopy, respectively. All the synthesized compounds were tested as inhibitors of Aβ toxicity toward pure cultures of rat cortical neurons.

Original languageEnglish
Pages (from-to)220-228
Number of pages9
JournalJournal of Peptide Science
Volume15
Issue number3
DOIs
Publication statusPublished - 2009

Keywords

  • β-sheet breaker peptides
  • Amyloid-β
  • Neuronal cultures
  • SFM
  • Thioflavin T
  • Trehalose

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    De Bona, P., Giuffrida, M. L., Caraci, F., Copani, A., Pignataro, B., Attanasio, F., Cataldo, S., Pappalardo, G., & Rizzarelli, E. (2009). Design and synthesis of new trehalose-conjugated pentapeptides as inhibitors of Aβ(1-42) fibrillogenesis and toxicity. Journal of Peptide Science, 15(3), 220-228. https://doi.org/10.1002/psc.1109