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Article

Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease

Faculty of Chemistry, “Al. I. Cuza” University of Iasi, 11 Carol I, 70605 Iasi, Romania
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Author to whom correspondence should be addressed.
Academic Editors: Luca D. D’Andrea and Lucia De Rosa
Molecules 2020, 25(19), 4536; https://doi.org/10.3390/molecules25194536
Received: 3 September 2020 / Revised: 22 September 2020 / Accepted: 2 October 2020 / Published: 3 October 2020
Aluminium (Al) is clearly neurotoxic and considerable evidence exists that Al may play a role in the aetiology or pathogenesis of Alzheimer’s disease (AD). Nevertheless, the link between AD pathology and Al is still open to debate. Therefore, we investigated here the interaction of aluminium ions with two Aβ peptide fragments and their analogues. First, we synthesised by the Fmoc/tBu solid-phase peptide synthesis (SPPS) strategy using an automated peptide synthesiser two new peptides starting from the Aβ(1–16) native peptide fragment. For this purpose, the three histidine residues (H6, H13, and H14) of the Aβ(1–16) peptide were replaced by three alanine and three serine residues to form the modified peptides Aβ(1–16)A36,13,14 and Aβ(1–16)S36,13,14 (primary structures: H-1DAEFRADSGYEVAAQK16-NH2 and H-1DAEFRSDSGYEVSSQK16-NH2). In addition, the Aβ(9–16) peptide fragment (H-9GYEVHHQK16-NH2) and its glycine analogues, namely Aβ(9–16)G110, (H-9GGEVHHQK16-NH2), Aβ(9–16)G213,14 (H-9GYEVGGQK16-NH2), and Aβ(9–16)G310,13,14 (H-9GGEVGGQK16-NH2), were manually synthesised in order to study Al binding to more specific amino acid residues. Both the peptides and the corresponding complexes with aluminium were comparatively investigated by mass spectrometry (MS), circular dichroism spectroscopy (CD), atomic force microscopy (AFM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR). Al–peptide molecular ions and Al-fragment ions were unambiguously identified in the MS and MS/MS spectra. AFM images showed dramatic changes in the film morphology of peptides upon Al binding. Our findings from the investigation of N-terminal 1-16 and even 9-16 normal and modified sequences of Aβ peptides suggest that they have the capability to be involved in aluminium ion binding associated with AD. View Full-Text
Keywords: amyloid-β peptides; modified Aβ peptide fragments; aluminium ions; metal binding; mass spectrometry; circular dichroism spectroscopy; atomic force microscopy; FT-IR; Alzheimer’s disease amyloid-β peptides; modified Aβ peptide fragments; aluminium ions; metal binding; mass spectrometry; circular dichroism spectroscopy; atomic force microscopy; FT-IR; Alzheimer’s disease
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MDPI and ACS Style

Mocanu, C.S.; Jureschi, M.; Drochioiu, G. Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease. Molecules 2020, 25, 4536. https://doi.org/10.3390/molecules25194536

AMA Style

Mocanu CS, Jureschi M, Drochioiu G. Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease. Molecules. 2020; 25(19):4536. https://doi.org/10.3390/molecules25194536

Chicago/Turabian Style

Mocanu, Cosmin S., Monica Jureschi, and Gabi Drochioiu. 2020. "Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease" Molecules 25, no. 19: 4536. https://doi.org/10.3390/molecules25194536

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