The metal loading ability of β-amyloid N-terminus: A combined potentiometric and spectroscopic study of copper(II) complexes with β-amyloid(1-16), its short or mutated peptide fragments, and its polyethylene glycol (PEG)-ylated analogue

Chiara A. Damante, Katalin Ösz, Zoltán Nagy, Giuseppe Pappalardo, Giulia Grasso, Giuseppe Impellizzeri, Enrico Rizzarelli, Imre Sóvágó

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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 Aβ could be involved in AD pathogenesis. In Aβ, 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 Aβ peptide fragment encompassing the 1-16 amino acid residues of the N-terminal region (Aβ(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 Aβ(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 Aβ, namely, Aβ(1-4), Aβ(1-6), AcAβ(1-6), and AcAβ(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.

Original languageEnglish
Pages (from-to)9669-9683
Number of pages15
JournalInorganic Chemistry
Volume47
Issue number20
DOIs
Publication statusPublished - Oct 20 2008

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ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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