Ac‐LPFFD‐Th: A Trehalose‐Conjugated Peptidomimetic as a Strong Suppressor of Amyloid‐β Oligomer Formation and Cytotoxicity. (7th July 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Chembiochem. Volume 17:Number 16(2016)
• Page Start: 1541
• Page End: 1549
• Publication Date: 2016-07-07
• Subjects: Alzheimer's disease -- amyloid beta-peptides -- inhibitors -- oligomers -- peptidomimetics -- trehalose; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600243
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: 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 α‐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 Aβ aggregation process was investigated by means of different biophysical techniques, including thioflavin T fluorescence, dynamic light scattering, ESI‐MS, and NMR spectroscopy. Moreover, we demonstrate that Ac‐LPFFD‐Th modifies the aggregation features of Aβ and protects neurons from Aβ oligomers' toxic insult. Abstract : Neuroprotective agents : Ac‐LPFFD‐Th prevents Aβ fibrillization, allows the survival of monomeric Aβ in solution. The compound protects the viability of cortical neurons exposed to toxic Aβ oligomers. A combined synergic action of the peptide/glycosyl moieties is envisaged. Evidence from this work provides insights for future design of neuroprotective agents.