Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of extracellular aggregates of amyloid-b peptides (Ab). Different metal ions accumulate within amyloid deposits, which suggests an involvement of metal ions in AD pathogenesis. Cu(II)-induced Ab neurotoxicity might result from changes in the coordination of the metal ion during Ab oligomerization or from different peptide/ metal ratios. Little is known on the Cu(II) complex with low-molecular-weight Ab species. Here, we report our results on the Cu(II) coordination modes with a synthetic Ab(1-16) dimer where the C-terminal 16Lys 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.
Copper(II) coordination properties of the A?(1-16)2 peptidomimetic: an experimental evidence of intermolecular macrochelate complex species in the A? dimer
Giuseppe Di Natale;Daniele Sanna;Giuseppe Pappalardo
2016
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of extracellular aggregates of amyloid-b peptides (Ab). Different metal ions accumulate within amyloid deposits, which suggests an involvement of metal ions in AD pathogenesis. Cu(II)-induced Ab neurotoxicity might result from changes in the coordination of the metal ion during Ab oligomerization or from different peptide/ metal ratios. Little is known on the Cu(II) complex with low-molecular-weight Ab species. Here, we report our results on the Cu(II) coordination modes with a synthetic Ab(1-16) dimer where the C-terminal 16Lys 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.