Faculty of Chemistry, "Al. I. Cuza" University of Iasi, 11 Carol I, 70605 Iasi, Romania.
Molecules. 2020 Oct 3;25(19):4536. doi: 10.3390/molecules25194536.
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/Bu solid-phase peptide synthesis (SPPS) strategy using an automated peptide synthesiser two new peptides starting from the Aβ native peptide fragment. For this purpose, the three histidine residues (H, H, and H) of the Aβ peptide were replaced by three alanine and three serine residues to form the modified peptides AβA and AβS (primary structures: H-DAEFRDSGYEVQK-NH and H-DAEFRDSGYEVQK-NH). In addition, the Aβ peptide fragment (H-GYEVHHQK-NH) and its glycine analogues, namely AβG, (H-GEVHHQK-NH), AβG (H-GYEVQK-NH), and AβG (H-GEVQK-NH), 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.
铝（Al）显然具有神经毒性，有大量证据表明，铝可能在阿尔茨海默病（AD）的病因或发病机制中起作用。然而，AD 病理学与铝之间的联系仍存在争议。因此，我们在这里研究了铝离子与两种 Aβ 肽片段及其类似物的相互作用。首先，我们使用自动化肽合成仪通过 Fmoc/Bu 固相肽合成（SPPS）策略合成了两种新的肽，其起始于 Aβ 天然肽片段。为此，Aβ 肽的三个组氨酸残基（H、H 和 H）被三个丙氨酸和三个丝氨酸残基取代，形成修饰肽 AβA 和 AβS（一级结构：H-DAEFRDSGYEVQK-NH 和 H-DAEFRDSGYEVQK-NH）。此外，还手动合成了 Aβ 肽片段（H-GYEVHHQK-NH）及其甘氨酸类似物，即 AβG（H-GEVHHQK-NH）、AβG（H-GYEVQK-NH）和 AβG（H-GEVQK-NH），以研究铝与更特定的氨基酸残基结合。通过质谱（MS）、圆二色光谱（CD）、原子力显微镜（AFM）、扫描电子显微镜（SEM）和傅里叶变换红外光谱（FT-IR）对肽及其与铝的相应配合物进行了比较研究。在 MS 和 MS/MS 谱中明确鉴定了铝-肽分子离子和铝-片段离子。AFM 图像显示，肽的薄膜形貌在与铝结合后发生了剧烈变化。我们对 Aβ 肽的 N 端 1-16 甚至 9-16 个正常和修饰序列的研究结果表明，它们具有与 AD 相关的参与铝离子结合的能力。
