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.
Bioinspired peptides are attractive biomolecules which can improve our understanding of self-assembly processes for rational design of new peptide-based materials. Herein, a new amidated peptide FRSAPFIE (FRS), based on a sequence present in human collagen, was synthesized, characterized by mass spectrometry and subjected to self-assembling investigations. The optimal conditions for self-assembly were disclosed by dynamic light scattering at 32 °C and a peptide concentration of 0.51 %. In addition, AFM studies revealed ellipsoidal FRS shapes with an area between 0.8 and 3.1 μm 2 . The ability of selfassembly was also proved using FAD dye as extrinsic fluorescence reporter. According to the theoretical analysis, the FRS peptide tends to form a bundle-type association, with a type of fibrillary tangles particle. Altogether, our findings address new challenges regarding the FRS peptide which can be used in further self-assembly studies to design biocompatible drug-delivery platforms.
Phenylketonuria is a serious genetic disease caused by a deficiency of phenylalanine metabolism, an essential amino acid found in daily nutrition. This disorder is caused by the lack of a specific enzyme called phenylalanine hydroxylase which mediates the conversion of phenylalanine to tyrosine). Thus, after ingestion of phenyl alanine-rich proteins, the amino acid concentration increases considerably in the blood due to proteolysis. Genetic deffects of enzymes responsible for phenylalanine metabolic conversion were intensively studied. Among them the defect of gene encoding phenylalanine hydroxylase has a higher notoriety. This genetic defect is translated in an inactive enzyme constructs that impair the aminoacid hydroxylation. This physiological stage is also called hyperphenylalaninemia where slightly high levels of phenylalanine are noticed in the blood or urine. Consequently, the amino acid is converted to phenylpyruvic acid by transamination, the later displaying a particularly toxic effect against brain tissues. The aim of this study was to quantify tyrosine in the blood of patients suffering of phenylketonuria by an alternative enzymatic method. The tyrosinase used in this assay was extracted from commercial mushrooms (Agaricus bisporus) following the Haghbeen protocol with some modifications. Two chromatographic steps (molecular exclusion chromatography and ionic exchange chromatography) were used during the enzyme purification process. High purity samples were concentrated using ultrafiltration. The tyrosinase was screened by a classical enzymatic microplate assay having DOPA as a substrate. Finally the pure enzyme was used in order to quantify tyrosine from different standard solutions. The level of tyrosine from deproteinized serum samples was determined using a similar enzymatic strategy.
Aggregation of amyloid-β peptides (Aβ) is a hallmark of Alzheimer’s disease (AD), which is affecting an increasing number of people. Hence, there is an urgent need to develop new pharmaceutical treatments which could be used to prevent the AD symptomatology. Activity-dependent neuroprotective protein (ADNP) was found to be deficient in AD, whereas NAP, an 8-amino-acid peptide (1NAPVSIPQ8) derived from ADNP, was shown to enhance cognitive function. The higher tendency of zinc ion to induce Aβ aggregation and formation of amorphous aggregates is also well-known in the scientific literature. Although zinc binding to Aβ peptides was extensively investigated, there is a shortage of knowledge regarding the relationship between NAP peptide and zinc ions. Therefore, here, we investigated the binding of zinc ions to the native NAP peptide and its analog obtained by replacing the serine residue in the NAP sequence with tyrosine (1NAPVYIPQ8) at various molar ratios and pH values by mass spectrometry (MS) and nuclear magnetic resonancespectroscopy (NMR). Matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry confirmed the binding of zinc ions to NAP peptides, while the chemical shift of Asp1, observed in 1H-NMR spectra, provided direct evidence for the coordinating role of zinc in the N-terminal region. In addition, molecular modeling has also contributed largely to our understanding of Zn binding to NAP peptides.
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