Copper(ii) coordination properties of the Aβ(1–16)2 peptidomimetic: experimental evidence of intermolecular macrochelate complex species in the Aβ dimer12. (7th November 2016)

• Record Type: Journal Article
• Authors: Di Natale, Giuseppe; Sinopoli, Alessandro; Grenács, Ágnes; Sanna, Daniele; Sóvágó, Imre; Pappalardo, Giuseppe
• Is Part Of: New journal of chemistry. Volume 40:Number 12(2016:Dec.)
• Page Start: 10274
• Page End: 10284
• Publication Date: 2016-11-07
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c6nj02354a
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : The coordination features of the copper(ii ) complexes with a Aβ(1–16)2 dimeric model are reported for the first time. Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of extracellular aggregates of amyloid-β peptides (Aβ). Different metal ions accumulate within amyloid deposits, which suggests an involvement of metal ions in AD pathogenesis. Cu(ii )-induced Aβ neurotoxicity might result from changes in the coordination of the metal ion during Aβ oligomerization or from different peptide/metal ratios. Little is known on the Cu(ii ) complex with low-molecular-weight Aβ species. Here, we report our results on the Cu(ii ) coordination modes with a synthetic Aβ(1–16) dimer where the C-terminal 16 Lys residue, of each peptide chain, is linked to a N, N -bis[(3-amino)propyl]glycine bearing a PEG moiety at the C-terminus. The formation of macrochelate complex species with the involvement of imidazole nitrogen donor atoms of His13 and His14, during copper(ii ) binding at physiological pH and low metal to peptide ratios, is observed.