Ac-LPFFD-Th: A Trehalose-Conjugated Peptidomimetic as a Strong Suppressor of Amyloid- Oligomer Formation and Cytotoxicity

作者：Sinopoli Alessandro; Giuffrida Alessandro; Tomasello Marianna Flora; Giuffrida Maria Laura; Leone Marilisa; Attanasio Francesco; Caraci Filippo; De Bona Paolo; Naletova Irina; Saviano Michele; Copani Agata; Pappalardo Giuseppe^*; Rizzarelli Enrico

来源：ChemBioChem, 2016, 17(16): 1541-1549.

DOI：10.1002/cbic.201600243

• Alzheimer's disease
• amyloid beta-peptides
• inhibitors
• oligomers
• peptidomimetics
• trehalose

The inhibition of amyloid formation is a promising therapeutic approach for the treatment of neurodegenerative diseases. Peptide-based inhibitors, which have been widely investigated, are generally derived from original amyloid sequences. Most interestingly, trehalose, a nonreducing disaccharide of -glucose, is effective in preventing the aggregation of numerous proteins. We have determined that the development of hybrid compounds could provide new molecules with improved properties that might synergically increase the potency of their single moieties. In this work, the ability of Ac-LPFFD-Th, a C-terminally trehalose-conjugated derivative, to slow down the A aggregation process was investigated by means of different biophysical techniques, including thioflavinT fluorescence, dynamic light scattering, ESI-MS, and NMR spectroscopy. Moreover, we demonstrate that Ac-LPFFD-Th modifies the aggregation features of A and protects neurons from Aoligomers' toxic insult.

• 出版日期2016-8-17