Metal loading capacity of aβ N-terminus: A combined potentiometrie and spectroscopic study of zinc(II) complexes with Aβ(1-16), its short or mutated peptide fragments and its polyethylene glycol-ylated analogue

Chiara A. Damante, K. Ősz, Zoltán Nagy, Giuseppe Pappalardo, Giulia Grasso, Giuseppe Impellizzeri, Enrico Rizzarelli, I. Sóvágó

Research output: Contribution to journalArticle

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Abstract

Aggregation of the amyloid β-peptide (Aβ) into insoluble fibrils is a key pathological event In Alzheimer's Disease (AD). There is now compelling evidence that metal binding to Aβ Is Involved In AD pathogenesis. The amino acid region 1-16 is widely considered as the metal binding domain of Aβ. In this work, we used a combined Potentiometrie, NMR, and electrospray ionization mass spectrometry (ESI-MS) approach to study the zinc(II) binding to a new polyethylene glycol (PEG)-conjugated peptide fragment encompassing the 1-16 amino acid sequence of β (β(1-16)PEG). Our results demonstrate for the first time that the Aβ(1 -16) is able to coordinate up to three zinc Ions, all the histldyl residues acting as Independent anchor sites. The study was complemented by systematically Investigating the zinc(II) complexes of a series of shorter peptide fragments related to the Aβ(1-16) sequence, namely, Aβ(1-4), Aβ(1 -6), AcAβ(I-O), AcAβ(8-16)Y10A. The comparison of the whole results allowed the identification of the zinc(ll) preferred binding sites within the longer Aβ(1-16) amino acid sequence. Unlike copper(II) that prefers the N-termlnal amino group as the main binding site, the zinc(II) is preferentially placed In the 8-16 amino acidic region of Aβ(1-16).

Original languageEnglish
Pages (from-to)10405-10415
Number of pages11
JournalInorganic Chemistry
Volume48
Issue number21
DOIs
Publication statusPublished - Nov 2 2009

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Peptide Fragments
peptides
Zinc
glycols
polyethylenes
zinc
Metals
fragments
analogs
amino acids
metals
Amino Acids
Binding Sites
pathogenesis
Electrospray ionization
Anchors
Amyloid
Mass spectrometry
Copper
mass spectroscopy

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Metal loading capacity of aβ N-terminus : A combined potentiometrie and spectroscopic study of zinc(II) complexes with Aβ(1-16), its short or mutated peptide fragments and its polyethylene glycol-ylated analogue. / Damante, Chiara A.; Ősz, K.; Nagy, Zoltán; Pappalardo, Giuseppe; Grasso, Giulia; Impellizzeri, Giuseppe; Rizzarelli, Enrico; Sóvágó, I.

In: Inorganic Chemistry, Vol. 48, No. 21, 02.11.2009, p. 10405-10415.

Research output: Contribution to journalArticle

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