Inhibition of amyloid peptide fragment Aβ 25-35 fibrillogenesis and toxicity by N-terminal β-amino acid-containing esapeptides: Is taurine moiety essential for in vivo effects?

Cesare Giordano, Anna Sansone, Annalisa Masi, Alessandra Masci, Luciana Mosca, Roberta Chiaraluce, Alessandra Pasquo, Valerio Consalvi

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Abstract

We report the synthesis and fibrillogenesis inhibiting activity of the new peptide derivatives 1-4, related to the pentapeptide Ac-LPFFD-NH 2 (iAβ5p), proposed by Soto and co-workers and widely recognized as one of the most active β-sheet breaker agents. The Aβ 25-35 fragment of the parent full-length Aβ 1-42 was used as fibrillogenesis model. The activity of peptide derivatives 1-4 was tested in vitro by thioflavin T binding assay, far UV CD spectroscopy, and scanning electron microscopy. Their ability to hinder the toxic effect of Aβ 25-35in vivo was studied by monitoring the viability of human SH-SY5Y neuroblastoma cells and the prevention of superoxide anion radical release from BV2 microglial cells. The results point to a favourable role in the fibrillogenesis inhibitory activity of the sulphonamide junction for compounds 1 and 2, containing an N, N-dimethyltaurine and a taurine amino-terminal moiety, respectively. Furthermore, compounds 1 and 2 show a significant protective effect on cell viability, rescuing the cells from the toxicity exerted by Aβ 25-35 treatment. The synthesis and in vivo/in vitro activity of the pseudopeptide analogues 1-4 as inhibitors of amyloid peptide frgment Aβ 25-35 fibrillogenesis and toxicity are reported. © 2011 John Wiley & Sons A/S.
Original languageEnglish
Pages (from-to)30 - 37
Number of pages8
JournalChemical Biology and Drug Design
Volume79
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

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