Transfer of Copper from an Amyloid to a Natural Copper‐Carrier Peptide with a Specific Mediating Ligand |
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| Authors: | Dr. Michel Nguyen Dr. Christian Bijani Nathalie Martins Prof. Dr. Bernard Meunier Dr. Anne Robert |
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| Affiliation: | 1. Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France);2. Université de Toulouse, Service Commun de Spectrométrie de Masse, 31077 Toulouse cedex 4 (France);3. Guangdong University of Technology, Department of Chemical Engineering, no. 100 Waihuan Xi road, Education Mega Center, Panyu District, Guangzhou (P. R. China) |
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| Abstract: | The oxidative stress that arises from the catalytic reduction of dioxygen by CuII/I‐loaded amyloids is the major pathway for neuron death that occurs in Alzheimer’s disease. In this work, we show that bis‐8(aminoquinoline) ligands, copper(II) specific chelators, are able to catalytically extract CuII from Cu–Aβ1–16 and then completely release CuI in the presence of glutathione to provide a CuI–glutathione complex, a biological intermediate that is able to deliver copper to apo forms of copper–protein complexes. These data demonstrate that bis‐8(aminoquinolines) can perform the transfer of copper ions from the pathological Cu–amyloid complexes to regular copper–protein complexes. These copper‐specific ligands assist GSH to recycle CuI in an AD brain and consequently slow down oxidative damage that is due to copper dysregulation in Alzheimer’s disease. Under the same conditions, we have shown that the copper complex of PBT2, a mono(8‐hydroxyquinoline) previously used as a drug candidate, does not efficiently release copper in the presence of GSH. In addition, we report that GSH itself was unable to fully abstract copper ions from Cu–β‐amyloid complexes. |
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| Keywords: | alzheimer’ s disease aminoquinoline chelates copper medicinal chemistry |
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