title: The metal loading ability of beta-amyloid N-terminus: a combined potentiometric and spectroscopic study of copper(II) complexes with beta-amyloid(1-16), its short or mutated peptide fragments, and its polyethylene glycol (PEG)-ylated analogue.
abstract: Alzheimer's disease (AD) is becoming a rapidly growing health problem, as it is one of the main causes of dementia in the elderly. Interestingly, copper(II) (together with zinc and iron) ions are accumulated in amyloid deposits, suggesting that metal binding to Abeta could be involved in AD pathogenesis. In Abeta, the metal binding is believed to occur within the N-terminal region encompassing the amino acid residues 1-16. In this work, potentiometric, spectroscopic (UV-vis, circular dichroism, and electron paramagnetic resonance), and electrospray ionization mass spectrometry (ESI-MS) approaches were used to investigate the copper(II) coordination features of a new polyethylene glycol (PEG)-conjugated Abeta peptide fragment encompassing the 1-16 amino acid residues of the N-terminal region (Abeta(1-16)PEG). The high water solubility of the resulting metal complexes allowed us to obtain a complete complex speciation at different metal-to-ligand ratios ranging from 1:1 to 4:1. Potentiometric and ESI-MS data indicate that Abeta(1-16)PEG is able to bind up to four copper(II) ions. Furthermore, in order to establish the coordination environment at each metal binding site, a series of shorter peptide fragments of Abeta, namely, Abeta(1-4), Abeta(1-6), AcAbeta(1-6), and AcAbeta(8-16)Y10A, were synthesized, each encompassing a potential copper(II) binding site. The complexation properties of these shorter peptides were also comparatively investigated by using the same experimental approach.
authors.affiliation: Department of Chemical Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
authors.forename: Chiara A
authors.initials: CA
authors.lastname: Damante
authors.forename: Katalin
authors.initials: K
authors.lastname: Osz
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Nagy
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
authors.forename: Giulia
authors.initials: G
authors.lastname: Grasso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Impellizzeri
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
authors.forename: Imre
authors.initials: I
authors.lastname: Sóvágó
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D011092:Polyethylene Glycols / Q000378:metabolism*; D011199:Potentiometry; D011487:Protein Conformation; D011522:Protons; D013057:Spectrum Analysis; D014867:Water / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011522:Protons; C433241:amyloid beta-protein (1-16); D014867:Water; D011092:Polyethylene Glycols; D003300:Copper