Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease
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 wi...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/19/4536 |
| _version_ | 1797551829131722752 |
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| author | Cosmin Stefan Mocanu Monica Jureschi Gabi Drochioiu |
| author_facet | Cosmin Stefan Mocanu Monica Jureschi Gabi Drochioiu |
| author_sort | Cosmin Stefan Mocanu |
| collection | DOAJ |
| description | 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/<i>t</i>Bu solid-phase peptide synthesis (SPPS) strategy using an automated peptide synthesiser two new peptides starting from the Aβ<sub>(1–16)</sub> native peptide fragment. For this purpose, the three histidine residues (H<sup>6</sup>, H<sup>13</sup>, and H<sup>14</sup>) of the Aβ<sub>(1–16)</sub> peptide were replaced by three alanine and three serine residues to form the modified peptides Aβ<sub>(1–16)</sub>A<sub>3</sub><sup>6,13,14</sup> and Aβ<sub>(1–16)</sub>S<sub>3</sub><sup>6,13,14</sup> (primary structures: H-<sup>1</sup>DAEFR<b>A</b>DSGYEV<b>AA</b>QK<sup>16</sup>-NH<sub>2</sub> and H-<sup>1</sup>DAEFR<b>S</b>DSGYEV<b>SS</b>QK<sup>16</sup>-NH<sub>2</sub>). In addition, the Aβ<sub>(9–16)</sub> peptide fragment (H-<sup>9</sup>GYEVHHQK<sup>16</sup>-NH<sub>2</sub>) and its glycine analogues, namely Aβ<sub>(9–16)</sub>G<sub>1</sub><sup>10</sup>, (H-<sup>9</sup>G<b>G</b>EVHHQK<sup>16</sup>-NH<sub>2</sub>), Aβ<sub>(9–16)</sub>G<sub>2</sub><sup>13,14</sup> (H-<sup>9</sup>GYEV<b>GG</b>QK<sup>16</sup>-NH<sub>2</sub>), and Aβ<sub>(9–16)</sub>G<sub>3</sub><sup>10,13,14</sup> (H-<sup>9</sup>G<b>G</b>EV<b>GG</b>QK<sup>16</sup>-NH<sub>2</sub>), 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. |
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| language | English |
| last_indexed | 2024-03-10T15:51:39Z |
| publishDate | 2020-10-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-484d41c50a8f4600b150be51ad9d8acb2023-11-20T15:59:23ZengMDPI AGMolecules1420-30492020-10-012519453610.3390/molecules25194536Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s DiseaseCosmin Stefan Mocanu0Monica Jureschi1Gabi Drochioiu2Faculty of Chemistry, “Al. I. Cuza” University of Iasi, 11 Carol I, 70605 Iasi, RomaniaFaculty of Chemistry, “Al. I. Cuza” University of Iasi, 11 Carol I, 70605 Iasi, RomaniaFaculty of Chemistry, “Al. I. Cuza” University of Iasi, 11 Carol I, 70605 Iasi, RomaniaAluminium (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/<i>t</i>Bu solid-phase peptide synthesis (SPPS) strategy using an automated peptide synthesiser two new peptides starting from the Aβ<sub>(1–16)</sub> native peptide fragment. For this purpose, the three histidine residues (H<sup>6</sup>, H<sup>13</sup>, and H<sup>14</sup>) of the Aβ<sub>(1–16)</sub> peptide were replaced by three alanine and three serine residues to form the modified peptides Aβ<sub>(1–16)</sub>A<sub>3</sub><sup>6,13,14</sup> and Aβ<sub>(1–16)</sub>S<sub>3</sub><sup>6,13,14</sup> (primary structures: H-<sup>1</sup>DAEFR<b>A</b>DSGYEV<b>AA</b>QK<sup>16</sup>-NH<sub>2</sub> and H-<sup>1</sup>DAEFR<b>S</b>DSGYEV<b>SS</b>QK<sup>16</sup>-NH<sub>2</sub>). In addition, the Aβ<sub>(9–16)</sub> peptide fragment (H-<sup>9</sup>GYEVHHQK<sup>16</sup>-NH<sub>2</sub>) and its glycine analogues, namely Aβ<sub>(9–16)</sub>G<sub>1</sub><sup>10</sup>, (H-<sup>9</sup>G<b>G</b>EVHHQK<sup>16</sup>-NH<sub>2</sub>), Aβ<sub>(9–16)</sub>G<sub>2</sub><sup>13,14</sup> (H-<sup>9</sup>GYEV<b>GG</b>QK<sup>16</sup>-NH<sub>2</sub>), and Aβ<sub>(9–16)</sub>G<sub>3</sub><sup>10,13,14</sup> (H-<sup>9</sup>G<b>G</b>EV<b>GG</b>QK<sup>16</sup>-NH<sub>2</sub>), 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.https://www.mdpi.com/1420-3049/25/19/4536amyloid-β peptidesmodified Aβ peptide fragmentsaluminium ionsmetal bindingmass spectrometrycircular dichroism spectroscopy |
| spellingShingle | Cosmin Stefan Mocanu Monica Jureschi Gabi Drochioiu Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease Molecules amyloid-β peptides modified Aβ peptide fragments aluminium ions metal binding mass spectrometry circular dichroism spectroscopy |
| title | Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease |
| title_full | Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease |
| title_fullStr | Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease |
| title_full_unstemmed | Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease |
| title_short | Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer’s Disease |
| title_sort | aluminium binding to modified amyloid β peptides implications for alzheimer s disease |
| topic | amyloid-β peptides modified Aβ peptide fragments aluminium ions metal binding mass spectrometry circular dichroism spectroscopy |
| url | https://www.mdpi.com/1420-3049/25/19/4536 |
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