title: Ac-LPFFD-Th: A Trehalose-Conjugated Peptidomimetic as a Strong Suppressor of Amyloid-β Oligomer Formation and Cytotoxicity.
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.
authors.affiliation: PhD Program in Translational Biomedicine, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sinopoli
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, Via P. Gaifami 18, 95126, Catania, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuffrida
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, Via P. Gaifami 18, 95126, Catania, Italy.
authors.forename: Marianna Flora
authors.initials: MF
authors.lastname: Tomasello
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, Via P. Gaifami 18, 95126, Catania, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Giuffrida
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Leone
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, Via P. Gaifami 18, 95126, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Attanasio
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 S. Euclid Avenue, Box 8231, St. Louis, MO, 63110, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Bona
authors.affiliation: Department of Biomedical Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
authors.forename: Irina
authors.initials: I
authors.lastname: Naletova
authors.affiliation: Institute of Crystallography, CNR, Via G. Amendola 122/O, 70126, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.affiliation: Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Copani
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, Via P. Gaifami 18, 95126, Catania, Italy. giuseppe.pappalardo@cnr.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
authors.affiliation: Institute of Biostructures and Bioimaging, CNR, Via P. Gaifami 18, 95126, Catania, Italy.|Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D014199:Trehalose / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D057786:Peptidomimetics; D014199:Trehalose
keywords: Alzheimer's disease; amyloid beta-peptides; inhibitors; oligomers; peptidomimetics; trehalose