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.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
Giordano, C., Sansone, A., Masi, A., Masci, A., Mosca, L., Chiaraluce, R., ... Consalvi, V. (2012). 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? Chemical Biology and Drug Design, 79(1), 30 - 37. https://doi.org/10.1111/j.1747-0285.2011.01259.x