Effects of oxidation on copper-binding properties of Aβ1-16 peptide: A pulse radiolysis study

Abstract

The reaction of hydroxyl radicals ((•)OH) with Aβ1-16 peptide was carried out using pulse radiolysis to understand the effect of oxidation of peptide on its copper-binding properties. This reaction produced oxidized, dimeric and trimeric Aβ1-16 peptide species. The formation of these products was established with the help of fluorescence spectroscopy and mass spectrometry. The mass spectral data indicate that the major site of oxidation is at His6, while the site for dimerization is at Tyr10. Diethyl pyrocarbonate-treated Aβ1-16 peptide did not produce any trimeric species upon oxidation with (•)OH. The quantitative chemical modification studies indicated that one of the three histidine residues is covalently modified during pulse radiolysis. The copper-binding studies of the oxidized peptide revealed that it has similar copper-binding properties as the unoxidized peptide. Further, the cytotoxicity studies point out that both oxidized and unoxidized Aβ1-16 peptide are equally efficient in producing free radicals in presence of copper and ascorbate that resulted in comparable cell death.

Metal complexes of amino acids and peptides

“…[193][194][195][196][197][198][199] The other compilations are devoted to specific aspects of the disease including an overview on the role of Cu(II) ions, 200 the description of the solution equilibria of Cu(II)-Ab interaction, 201 the possible role of redox chemistry and ROS production [202][203][204][205] and on the inorganic perspectives of neutrophins in AD. 234 The pH-dependence of the oxidative stress caused by the Cu(II)-amyloid species was evaluated in another report. [207][208][209] The highest ratio of the most recent studies is dealing with the involvement of Cu(II) ions in the development or treatment of AD.…”

One-pot synthesis and evaluation of novel 3-aryl-6-ethoxycarbonyl-4-hydroxy-2H-pyran-2-one as a potent cytotoxic agent

“…Cell viability was measured in 96-well plates by quantitative colorimetric assay using MTT. 16 Briey, 10 5 cells per mL were seeded in 96-well plates for assay. The compounds were dissolved in DMSO and were diluted to the desired concentrations using plain DMEM.…”

Fluorescent Copper Probe Inhibiting Aβ1–16-Copper(II)-Catalyzed Intracellular Reactive Oxygen Species Production

“…In addition to this, ROS reacts with Aβ to produce toxic oxidation products such as dimer, trimer, etc. 8 Copper is known to enhance peptide aggregation kinetics, leading to amyloid plaque formation in the brain, which is one of the hallmarks of AD. 3 Thus, copper plays a crucial role in the neurodegeneration and progression of AD.…”

“…The uninterrupted shuttling of copper bound to Aβ results in the generation of ROS extracellularly. In addition to this, ROS reacts with Aβ to produce toxic oxidation products such as dimer, trimer, etc . Copper is known to enhance peptide aggregation kinetics, leading to amyloid plaque formation in the brain, which is one of the hallmarks of AD .…”

“…The above findings suggest that OBEP-CS1 inhibits Aβ1−16-Cu II -catalyzed ROS generation. The ROS generated, such as hydroxyl radicals ( • OH), can further react with Aβ, which leads to the formation of toxic oxidation products of Aβ and oligomeric species. , The effects of OBEP-CS1 on the copper-catalyzed oxidation of Aβ1–16 and on the formation of oxidation products were analyzed using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS; see the Supporting Information for details). Aβ1–16-Cu II was reduced to Aβ1–16-Cu I species by ascorbic acid and then allowed to oxidize back to Aβ1–16-Cu II in the presence of atmospheric oxygen.…”