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1. Restoring cellular copper homeostasis in Alzheimer disease: a novel peptide shuttle is internalized by an ATP-dependent endocytosis pathway involving Rab5- and Rab14-endosomes

Author

Michael Okafor, Olivia Champomier, Laurent Raibaut, Sebahat Ozkan, Naima El Kholti, Stéphane Ory, Sylvette Chasserot-Golaz, Stéphane Gasman, Christelle Hureau, Peter Faller, and Nicolas Vitale

Subjects
Alzheimer’s disease, copper homeostasis, endocytosis, endolysosomes, rab GTPase, Biology (General), QH301-705.5
Abstract

CPPs, or Cell-Penetrating Peptides, offer invaluable utility in disease treatment due to their ability to transport various therapeutic molecules across cellular membranes. Their unique characteristics, such as biocompatibility and low immunogenicity, make them ideal candidates for delivering drugs, genes, or imaging agents directly into cells. This targeted delivery enhances treatment efficacy while minimizing systemic side effects. CPPs exhibit versatility, crossing biological barriers and reaching intracellular targets that conventional drugs struggle to access. This capability holds promise in treating a wide array of diseases, including cancer, neurodegenerative disorders, and infectious diseases, offering a potent avenue for innovative and targeted therapies, yet their precise mechanism of cell entry is far from being fully understood. In order to correct Cu dysregulation found in various pathologies such as Alzheimer disease, we have recently conceived a peptide Cu(II) shuttle, based on the αR5W4 CPP, which, when bound to Cu(II), is able to readily enter a neurosecretory cell model, and release bioavailable Cu in cells. Furthermore, this shuttle has the capacity to protect cells in culture against oxidative stress-induced damage which occurs when Cu binds to the Aβ peptide. The aim of this study was therefore to characterize the cell entry route used by this shuttle and determine in which compartment Cu is released. Pharmacological treatments, siRNA silencing and colocalization experiments with GFP-Rab fusion proteins, indicate that the shuttle is internalized by an ATP-dependent endocytosis pathway involving both Rab5 and Rab14 endosomes route and suggest an early release of Cu from the shuttle.

Published
2024
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3. Effect of Metal Environment and Immobilization on the Catalytic Activity of a Cu Superoxide Dismutase Mimic

Author

Micaela Richezzi, Joaquín Ferreyra, Sharon Signorella, Claudia Palopoli, Gustavo Terrestre, Nora Pellegri, Christelle Hureau, and Sandra R. Signorella

Subjects
Cu-based SOD mimic, structure, mesoporous silica, click chemistry, SOD activity, Inorganic chemistry, QD146-197
Abstract

The Cu(II)/Cu(I) conversion involves variation in the coordination number and geometry around the metal center. Therefore, the flexibility/rigidity of the ligand plays a critical role in the design of copper superoxide dismutase (SOD) mimics. A 1,3-Bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), a flexible ligand with an N4-donor set, was used to prepare [Cu(pypapn)(ClO4)2], a trans-Cu(II) complex whose structure was determined by the X-ray diffraction. In DMF or water, perchlorate anions are exchanged with solvent molecules, affording [Cu(pypan)(solv)2]2+ that catalyzes O2•− dismutation with a second-order rate constant kMcF = 1.26 × 107 M−1 s−1, at pH 7.8. This high activity results from a combination of ligand flexibility, total charge, and labile binding sites, which places [Cu(pypapn)(solv)2]2+ above other mononuclear Cu(II) complexes with more favorable redox potentials. The covalent anchoring of the alkyne group of the complex to azide functionalized mesoporous silica through “click” chemistry resulted in the retention of the SOD activity and improved stability. A dicationic Cu(II)-N4-Schiff base complex encapsulated in mesoporous silica was also tested as an SOD mimic, displaying higher activity than the free complex, although lower than [Cu(pypapn)(solv)2]2+. The robustness of covalently attached or encapsulated doubly charged Cu(II) complexes in a mesoporous matrix appears as a suitable approach for the design of copper-based hybrid catalysts for O2•− dismutation under physiological conditions.

Published
2023
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4. Synthesis, Characterization, and Biological Properties of the Copper(II) Complexes with Novel Ligand: N-[4-({2-[1-(pyridin-2-yl)ethylidene]hydrazinecarbothioyl}amino)phenyl]acetamide

Author

Roman Rusnac, Olga Garbuz, Yurii Chumakov, Victor Tsapkov, Christelle Hureau, Dorin Istrati, and Aurelian Gulea

Subjects
coordination compound, thiosemicarbazone, crystal structure, antioxidant activity, antimicrobial activity, antifungal activity, Inorganic chemistry, QD146-197
Abstract

For the first time, a thiosemicarbazone-type ligand containing a paracetamol structural unit was synthesized. Five new coordination compounds based on copper(II) salts: [Cu(L)CH3COO] (1), [{Cu(L)Cl}2]·H2O (2), [Cu(L)H2O·DMF]NO3 (3), [Cu(L)Br] (4), [Cu(L)H2O]ClO4 (5), were obtained, where HL is N-[4-({2-[1-(pyridin-2-yl)ethylidene]hydrazinecarbothioyl}amino)phenyl]acetamide. The new HL was characterized by NMR, FTIR, spectroscopy, and X-ray crystallography. All copper(II) coordination compounds were characterized by elemental analysis, FTIR, EPR spectroscopy, and molar electrical conductivity. Furthermore, single crystal X-ray diffraction analysis elucidated the structures of thiosemicarbazone HL as well as complexes 1–3. All compounds were tested for antimicrobial, antifungal, and antioxidant activities, and their toxicity to Daphnia magna was studied. Biological evaluation has revealed that most of the synthesized compounds demonstrate promising antibacterial, antifungal, and antioxidant activities. In many cases, their antibacterial/antifungal activity is comparable to that of certain drugs used in medicine for these purposes, and in some cases, even surpasses them. HL and complexes 2–5 exhibit antioxidant activity that surpasses that of Trolox. Furthermore, HL and complex 2 display virtually no toxicity to D. magna.

Published
2023
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6. The Critical Role of Ligand Flexibility on the Activity of Free and Immobilized Mn Superoxide Dismutase Mimics

Author

Micaela Richezzi, Sharon Signorella, Claudia Palopoli, Nora Pellegri, Christelle Hureau, and Sandra R. Signorella

Subjects
Mn bioinspired catalysts, mesoporous silica, click chemistry, encapsulation, SOD activity, Inorganic chemistry, QD146-197
Abstract

In low-molecular-weight Mn superoxide dismutase (SOD) mimics, the ligand plays a key role in tuning the reactivity of the metal center with O2•−. We used three ligands differing in their donor sites, flexibility and/or charge, to compare the redox properties and SOD activity of the resulting Mn complexes: 1,3-bis[(pyridin-2-ylmethyl)(propargyl)amino]propane (pypapn), 1,3-bis(pyridin-2-ylmethyleneamino)propane (py2pn) and 1,4-bis(salicylidenamino)butane (H2salbn). These ligands afford Mn complexes that, in aqueous solution, exist as mononuclear species [Mn(II)(pypapn)(H2O)2]2+, [Mn(II)(py2pn)(H2O)2]2+ and [Mn(III)(salbn)(H2O)2]+. The relative reactivity of these compounds with O2•− at pH 7.8, [Mn(pypapn)(H2O)2]2+ > [Mn(salbn)(H2O)2]+ > [Mn(py2pn)(H2O)2]2+, is independent of the redox potential but strongly depends on the ligand flexibility which becomes a critical feature when the reaction occurs through an inner-sphere electron-transfer mechanism. Immobilization was used to isolate and protect the catalyst from dissociation or dimerization during catalysis. [Mn(pypapn)(H2O)2]2+, with the alkyne group, was covalently grafted to azide functionalized mesoporous silica through click chemistry, while [Mn(py2pn)(solv)2]2+ and [Mn(salbn)(solv)2]+ were encapsulated in SBA-15 mesoporous silica through ionic exchange. The retention or enhancement of the SOD activity and the improved stability of the covalently attached catalyst and the doubly charged complex encapsulated in the silica pores, make them suitable for use in aqueous media.

Published
2023
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7. Synthesis, Structure, and Biologic Activity of Some Copper, Nickel, Cobalt, and Zinc Complexes with 2-Formylpyridine N4-Allylthiosemicarbazone

Author

Vasilii Graur, Yurii Chumakov, Olga Garbuz, Christelle Hureau, Victor Tsapkov, and Aurelian Gulea

Subjects
Biotechnology, TP248.13-248.65, Inorganic chemistry, QD146-197
Abstract

A series of zinc(II) ([Zn(H2O)(L)Cl] (1)), copper (II) ([Cu(L)Cl] (2), [Cu(L)Br] (3), [Cu2(L)2(CH3COO)2]·4H2O (4)), nickel(II) ([Ni(HL)2]Cl2·H2O (5)), and cobalt(III) ([Co(L)2]Cl (6)) complexes were obtained with 2-formylpyridine N4-allylthiosemicarbazone (HL). In addition another two thiosemicarbazones (3-formylpyridine N4-allylthiosemicarbazone (HLa) and 4-formylpyridine N4-allylthiosemicarbazone (HLb)) have been obtained. The synthesized thiosemicarbazones have been studied using 1H and 13C NMR spectroscopy, IR spectroscopy, and X-ray diffraction analysis. The composition and structure of complexes were studied using elemental analysis, IR and UV-Vis spectroscopies, molar conductivity, and magnetic susceptibility measurements. Single crystal X-ray diffraction analysis elucidated the structure of thiosemicarbazones HL, HLa, and HLb, as well as complexes 4 and 5. The antiproliferative properties of these compounds toward a series of cancer cell lines (HL-60, HeLa, BxPC-3, RD) and a normal cell line (MDCK) have been investigated. The nickel complex shows high selectivity (SI > 1000) toward HL-60 cell line and is the least toxic. The zinc complex shows the highest selectivity toward RD cell line (SI = 640). The copper complexes (2–4) are the most active molecular inhibitors of proliferation of cancer cells, but exhibit not such a high selectivity and are significantly more toxic. Zinc and copper complexes manifest high antibacterial activity. It was found that calculated at B3LYP level of theory different reactivity descriptors of studied compounds strongly correlate with their biological activity.

Published
2022
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8. Oxidative Damages on the Alzheimer’s Related-Aβ Peptide Alters Its Ability to Assemble

Author

Clémence Cheignon, Fabrice Collin, Laurent Sabater, and Christelle Hureau

Subjects
oxidative stress, peptide, assembly, copper, zinc, Therapeutics. Pharmacology, RM1-950
Abstract

Oxidative stress that can lead to oxidation of the amyloid-β (Aβ) peptide is considered a key feature in Alzheimer’s disease (AD), influencing the ability of Aβ to assemble into β-sheet rich fibrils that are commonly found in senile plaques of AD patients. The present study aims at investigating the fallouts of Aβ oxidation on the assembly properties of the Aβ peptide. To accomplish this, we performed kinetics and analysis on an oxidized Aβ (oxAβ) peptide, resulting from the attack of reactive oxygen species (ROS) that are formed by the biologically relevant Cu/Aβ/dioxygen/ascorbate system. oxAβ was still able to assemble but displayed ill-defined and small oligomeric assemblies compared to the long and thick β-sheet rich fibrils from the non-oxidized counterpart. In addition, oxAβ does affect the assembly of the parent Aβ peptide. In a mixture of the two peptides, oxAβ has a mainly kinetic effect on the assembly of the Aβ peptide and was able to slow down the formation of Aβ fibril in a wide pH range [6.0–7.4]. However, oxAβ does not change the quantity and morphology of the Aβ fibrils formed to a significant extent. In the presence of copper or zinc di-cations, oxAβ assembled into weakly-structured aggregates rather than short, untangled Cu-Aβ fibrils and long untangled Zn-Aβ fibrils. The delaying effect of oxAβ on metal altered Aβ assembly was also observed. Hence, our results obtained here bring new insights regarding the tight interconnection between (i) ROS production leading to Aβ oxidation and (ii) Aβ assembly, in particular via the modulation of the Aβ assembly by oxAβ. It is the first time that co-assembly of oxAβ and Aβ under various environmental conditions (pH, metal ions …) are reported.

Published
2023
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9. Sequence–Activity Relationship of ATCUN Peptides in the Context of Alzheimer’s Disease

Author

Margot Lefèvre, Kyangwi P. Malikidogo, Charlène Esmieu, and Christelle Hureau

Subjects
ATCUN peptide, copper, reactive oxygen species, kinetics, Organic chemistry, QD241-441
Abstract

Amino-terminal CuII and NiII (ATCUN) binding sequences are widespread in the biological world. Here, we report on the study of eight ATCUN peptides aimed at targeting copper ions and stopping the associated formation of reactive oxygen species (ROS). This study was actually more focused on Cu(Aβ)-induced ROS production in which the Aβ peptide is the “villain” linked to Alzheimer’s disease. The full characterization of CuII binding to the ATCUN peptides, the CuII extraction from CuII(Aβ), and the ability of the peptides to prevent and/or stop ROS formation are described in the relevant biological conditions. We highlighted in this research that all the ATCUN motifs studied formed the same thermodynamic complex but that the addition of a second histidine in position 1 or 2 allowed for an improvement in the CuII uptake kinetics. This kinetic rate was directly related to the ability of the peptide to stop the CuII(Aβ)-induced production of ROS, with the most efficient motifs being HWHG and HGHW.

Published
2022
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11. Why the Ala-His-His Peptide Is an Appropriate Scaffold to Remove and Redox Silence Copper Ions from the Alzheimer’s-Related Aβ Peptide

Author

Paulina Gonzalez, Laurent Sabater, Emilie Mathieu, Peter Faller, and Christelle Hureau

Subjects
ATCUN, copper, amyloid-β, peptides, ROS, kinetics, Microbiology, QR1-502
Abstract

The progressive, neurodegenerative Alzheimer’s disease (AD) is the most widespread dementia. Due to the ageing of the population and the current lack of molecules able to prevent or stop the disease, AD will be even more impactful for society in the future. AD is a multifactorial disease, and, among other factors, metal ions have been regarded as potential therapeutic targets. This is the case for the redox-competent Cu ions involved in the production of reactive oxygen species (ROS) when bound to the Alzheimer-related Aβ peptide, a process that contributes to the overall oxidative stress and inflammation observed in AD. Here, we made use of peptide ligands to stop the Cu(Aβ)-induced ROS production and we showed why the AHH sequence is fully appropriate, while the two parents, AH and AAH, are not. The AHH peptide keeps its beneficial ability against Cu(Aβ)-induced ROS, even in the presence of ZnII-competing ions and other biologically relevant ions. The detailed kinetic mechanism by which AHH could exert its action against Cu(Aβ)-induced ROS is also proposed.

Published
2022
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12. Reproducibility Problems of Amyloid-β Self-Assembly and How to Deal With Them

Author

Peter Faller and Christelle Hureau

Subjects
amyloid, peptide, reproducibility, self-assembly, aggregation, Chemistry, QD1-999
Abstract

The self-assembly of peptides and proteins into amyloid fibrils and other aggregates are linked to several diseases. One of the most studied cases is the peptide amyloid-β (Aβ), found self-assembled in Alzheimer's disease patients' brains. In test tubes, assays with chemically synthesized or recombinant Aβ are widely investigated to understand the aggregation process and to find modulators, which could be of therapeutic interest. Experience over more than a decade in our laboratory through discussions with colleagues, expertly studying the literature, and as reviewers revealed to us the widely encountered difficulty to control the aggregation and obtain reproducible results in the test tube. However, this issue is scarcely reported and discussed in the publications, which we think hampers strongly the progress in this field and can deceive newcomers. Here, we describe the difficulty and potential reasons to obtain reproducible aggregation data and propose some guidelines for working with it.

Published
2021
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13. Hybrid Bis-Histidine Phenanthroline-Based Ligands to Lessen Aβ-Bound Cu ROS Production: An Illustration of Cu(I) Significance

Author

Marielle Drommi, Clément Rulmont, Charlène Esmieu, and Christelle Hureau

Subjects
Alzheimer’s disease, copper, amyloid-β, ROS production, peptide, phenanthroline, Organic chemistry, QD241-441
Abstract

We here report the synthesis of three new hybrid ligands built around the phenanthroline scaffold and encompassing two histidine-like moieties: phenHH, phenHGH and H’phenH’, where H correspond to histidine and H’ to histamine. These ligands were designed to capture Cu(I/II) from the amyloid-β peptide and to prevent the formation of reactive oxygen species produced by amyloid-β bound copper in presence of physiological reductant (e.g., ascorbate) and dioxygen. The amyloid-β peptide is a well-known key player in Alzheimer’s disease, a debilitating and devasting neurological disorder the mankind has to fight against. The Cu-Aβ complex does participate in the oxidative stress observed in the disease, due to the redox ability of the Cu(I/II) ions. The complete characterization of the copper complexes made with phenHH, phenHGH and H’phenH’ is reported, along with the ability of ligands to remove Cu from Aβ, and to prevent the formation of reactive oxygen species catalyzed by Cu and Cu-Aβ, including in presence of zinc, the second metal ions important in the etiology of Alzheimer’s disease. The importance of the reduced state of copper, Cu(I), in the prevention and arrest of ROS is mechanistically described with the help of cyclic voltammetry experiments.

Published
2021
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14. N,N′-Bis(4-bromophenyl)-N,N′-dimethylurea

Author

Alexandre Pocinho, Sonia Mallet-Ladeira, Christelle Hureau, and Emmanuel Gras

Subjects
crystal structure, urea, folding, instability on storage, Crystallography, QD901-999
Abstract

The structure of the title compound, C15H14Br2N2O, at 180 K has monoclinic (P21/n) symmetry. It was obtained unexpectedly from the decomposition of the parent 4-bromo-N-tert-butoxycarbonyl-N-methyl-aniline. It exhibits an `endo' conformation with angles between the two aromatic rings slightly lower than the average values found for similar compounds on the Cambridge Structural Database. In the crystal, C—H...O hydrogen bonds and short Br...Br halogen bonds [3.444 (1) Å] are observed.

Published
2018
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16. A Robust and Efficient Production and Purification Procedure of Recombinant Alzheimers Disease Methionine-Modified Amyloid-β Peptides.

Author

Marie Hoarau, Yannick Malbert, Romain Irague, Christelle Hureau, Peter Faller, Emmanuel Gras, Isabelle André, and Magali Remaud-Siméon

Subjects
Medicine, Science
Abstract

An improved production and purification method for Alzheimer's disease related methionine-modified amyloid-β 1-40 and 1-42 peptides is proposed, taking advantage of the formation of inclusion body in Escherichia coli. A Thioflavin-S assay was set-up to evaluate inclusion body formation during growth and optimize culture conditions for amyloid-β peptides production. A simple and fast purification protocol including first the isolation of the inclusion bodies and second, two cycles of high pH denaturation/ neutralization combined with an ultrafiltration step on 30-kDa cut-off membrane was established. Special attention was paid to purity monitoring based on a rational combination of UV spectrophotometry and SDS-PAGE analyses at the various stages of the process. It revealed that this chromatography-free protocol affords good yield of high quality peptides in term of purity. The resulting peptides were fully characterized and are appropriate models for highly reproducible in vitro aggregation studies.

Published
2016
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19. Ability of Azathiacyclen Ligands To Stop Cu(Aβ)‐Induced Production of Reactive Oxygen Species: [3N1S] Is the Right Donor Set

Author

Kyangwi P. Malikidogo, Marielle Drommi, Elena Atrián‐Blasco, Jan Hormann, Nora Kulak, Charlène Esmieu, Christelle Hureau, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Freie Universität Berlin, Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), ANR-20-CE07-0009,Copperation,Ligands fluorescents: pour la conception rationnelle de ligands ciblant les ions cuivre dans le cadre de la maladie d'Alzheimer(2020), European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Physiochimie des Métaux (PMB), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Instituto de Nanociencia y Materiales de Aragón (INMA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad de Zaragossa, and Institut für Chemie und Biochemie, Anorganische Chemie, Freie Universität Berlin

Subjects
Oxidative stress, Organic Chemistry, Alzheimer, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [CHIM.COOR]Chemical Sciences/Coordination chemistry, EPR, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, General Chemistry, Alzheimer's disease, Macrocycles, Copper, Catalysis
Abstract

International audience; Alzheimer's disease (AD) is an incurable neurodegenerative disease that leads to the progressive and irreversible loss of mental functions. The amyloid beta (A beta) peptide involved in the disease is responsible for the production of damaging reactive oxygen species (ROS) when bound to Cu ions. A therapeutic approach that consists of removing Cu ions from A beta to alter this deleterious interaction is currently being developed. In this context, we report the ability of five different 12-membered thiaazacyclen ligands to capture Cu from A beta and to redox silence it. We propose that the presence of a sole sulfur atom in the ligand increases the rate of Cu capture and removal from A beta, while the kinetic aspect of the chelation was an issue encountered with the 4N parent ligand. The best ligand for removing Cu from A beta and inhibiting the associated ROS production is the 1-thia-4,7,10-triazacyclododecane [3N1S]. Indeed the replacement of more N by S atoms makes the corresponding Cu complexes easier to reduce and thus able to produce ROS on their own. In addition, the ligand with three sulfur atoms has a weaker affinity for Cu-II than A beta, and is thus unable to remove Cu from CuA beta.

Published
2023
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21. Development of Cu( ii )-specific peptide shuttles capable of preventing Cu–amyloid beta toxicity and importing bioavailable Cu into cells

Author

Michael Okafor, Paulina Gonzalez, Pascale Ronot, Islah El Masoudi, Anne Boos, Stéphane Ory, Sylvette Chasserot-Golaz, Stéphane Gasman, Laurent Raibaut, Christelle Hureau, Nicolas Vitale, Peter Faller, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), ANR-19-CE44-0019,PA-Box,Etude des fonctions pléiotropiques de l'acide phosphatidique dans la sécrétion régulée à l'aide d'une nouvelle boite à outils moléculaires(2019), and European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015)

Subjects
[CHIM.COOR]Chemical Sciences/Coordination chemistry, General Chemistry
Abstract

Copper (Cu) in its ionic forms is an essential element for mammals and its homeostasis is tightly controlled. Accordingly, Cu-dyshomeostasis can be lethal as is the case in the well-established genetic Wilson's and Menkes diseases. In Alzheimer's disease (AD), Cu-accumulation occurs in amyloid plaques, where it is bound to the amyloid-beta peptide (Aβ).

Published
2022
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22. The Aggregation Pattern of Aβ 1–40 is Altered by the Presence of N ‐Truncated Aβ 4–40 and/or Cu II in a Similar Way through Ionic Interactions

Author

Elena Atrián-Blasco, Wojciech Bal, Ewelina Stefaniak, Wojciech Goch, Christelle Hureau, and Laurent Sabater

Subjects
010405 organic chemistry, Chemistry, Organic Chemistry, Ionic bonding, chemistry.chemical_element, General Chemistry, 010402 general chemistry, Fibril, 01 natural sciences, Copper, Catalysis, 0104 chemical sciences, N-terminus, Fibril formation, Biophysics, Extracellular
Abstract

Alzheimer's disease (AD) is one of the most common of the multifactorial diseases and is characterized by a range of abnormal molecular processes, such as the accumulation of extracellular plaques containing the amyloid-β (Aβ) peptides and dyshomeostasis of copper in the brain. In this study, we have investigated the effect of CuII on the aggregation of Aβ1-40 and Aβ4-40 , representing the two most prevalent families of Aβ peptides, that is, the full length and N-truncated peptides. Both families are similarly abundant in healthy and AD brains. For either of the studied peptides, substoichiometric CuII concentrations accelerated aggregation, whereas superstoichiometric CuII inhibited fibril formation, likely by stabilizing the oligomers. The addition of either Aβ4-40 or substoichiometric CuII affected the aggregation profile of Aβ1-40 , by yielding shorter and thicker fibrils; amorphous aggregates were formed in the presence of a molar excess of CuII . The similarity of these two effects can be attributed to the increase in the positive charge on the Aβ N terminus, caused both by CuII complexation and N truncation at position 4. Our findings provide a better understanding of the biological Aβ aggregation process as these two Aβ species and CuII coexist and interact under physiological conditions.

Published
2021
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23. The aroylhydrazone INHHQ prevents memory impairment induced by Alzheimer’s-linked amyloid-β oligomers in mice

Author

Nicolás A. Rey, Elena Atrián-Blasco, Anna De Falco, Grasielle C. Kincheski, Sergio T. Ferreira, Christelle Hureau, Pontifical Catholic University of Rio de Janeiro (PUC), Institute of Biophysics Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro (UFRJ), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), National Institute for Translational Neuroscience/Brazil, Brazilian agencies Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Peptide, Pharmacology, Neuroprotection, Amyloid beta-Protein Precursor, Mice, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Isoniazid, medicine, Animals, Memory impairment, Amyloid-β oligomers, Senile plaques, chemistry.chemical_classification, Memory Disorders, Reactive oxygen species, Amyloid beta-Peptides, Hydrazones, Neurotoxicity, Brain, medicine.disease, 3. Good health, 030227 psychiatry, Disease Models, Animal, Psychiatry and Mental health, Neuroprotective Agents, chemistry, Toxicity, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Systemic administration, Rat, Metal-protein attenuating compounds, Oxidation-Reduction, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract

International audience; Converging evidence indicates that neurotoxicity and memory impairment in Alzheimer's disease is induced by brain accumulation of soluble amyloid-β oligomers (AβOs). Physiological metals are poorly distributed and concentrated in the senile plaques typical of Alzheimer's disease, where they may be coordinated to the amyloid-β peptide (Aβ). Indeed, zinc and copper increase Aβ oligomerization and toxicity. Metal-protein attenuating compounds represent a class of agents proposed for Alzheimer's disease treatment, as they reduce abnormal interactions of metal ions with Aβ, inhibit Aβ oligomerization and prevent deleterious redox reactions in the brain. The present work investigates the protective action of an isoniazid-derived aroylhydrazone, INHHQ, on AβO-induced memory impairment. Systemic administration of a single dose of INHHQ (1 mg/kg) prevented both short-term and long-term memory impairment caused by AβOs in mice. In-vitro studies showed that INHHQ prevents Cu(Aβ)-catalyzed production of reactive oxygen species. Although the mechanism of protection by INHHQ is not yet fully understood at a molecular level, the results reported herein certainly point to the value of aroylhydrazones as promising neuroprotective agents in Alzheimer's disease and related disorders.

Published
2020
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25. Keggin-type polyoxometalates as Cu(II) chelators in the context of Alzheimer's disease

Author

Elena Atrián-Blasco, Lucie de Cremoux, Xudong Lin, Rufus Mitchell-Heggs, Laurent Sabater, Sébastien Blanchard, Christelle Hureau, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Instituto de Nanociencia y Materiales de Aragón (INMA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad de Zaragossa, Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015)

Subjects
Anions, animal structures, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Catalysis, Alzheimer Disease, mental disorders, Materials Chemistry, Humans, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Chelating Agents, Amyloid beta-Peptides, 010405 organic chemistry, Metals and Alloys, General Chemistry, Polyelectrolytes, 0104 chemical sciences, 3. Good health, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Ceramics and Composites, sense organs, Reactive Oxygen Species, Copper
Abstract

Two Keggin polyoxometalates were used as new copper ligands to counteract the effects of CuII(Amyloid-β) interaction. Their ability to remove CuII from CuII(Amyloid-β), to stop CuII(Amyloid-β) induced formation of reactive oxygen species and to restore apo-like self-assembly of CuII(Amyloid-β) was shown.

Published
2022
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26. Versatile Activity of a Copper(II) Complex Bearing a N 4 ‐Tetradentate Schiff Base Ligand with Reduced Oxygen Species

Author

Micaela Richezzi, Joaquín Ferreyra, Juan Puzzolo, Lisandro Milesi, Claudia M. Palopoli, Diego M. Moreno, Christelle Hureau, Sandra R. Signorella, Instituto de Química Rosario (IQUIR), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Bioquımicas y Farmaceuticas [Rosario] (FBIOyF), Universidad Nacional de Rosario [Santa Fe]-Universidad Nacional de Rosario [Santa Fe], Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), National University of Rosario (PIP BIO553), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP 0337 and PUE 0068), Centre National de la Recherche Scientifique (CNRS, PICS 07121), and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT PICT-2019-03276)

Subjects
Inorganic Chemistry, Kinetics, Reactive intermediates, Superoxides, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Copper, Peroxides
Abstract

International audience; The reactivity of the Cu(II) complex of N,N’-bis(pyridin-2-ylmethylene)propane-1,3-diamine (py2pn), [Cu(py2pn)(ClO4)2], toward O2.− and H2O2 has been examined. The complex reacts with O2.− with fast second order kinetics, kMcF=4.05×106 M−1 s−1, employing the Cu(II)/Cu(I) couple proved by spectroscopic detection of the reduced form at low temperature. At −40 °C in DMF, the reaction of the complex with H2O2/Et3N yields an stable end-on Cu(II)-hydroperoxide, with kOOH=0.31 min−1, the formation of which has been established by DFT calculations, electronic and EPR spectra. At room temperature, the end-on Cu(II)-hydroperoxide reacts with a second Cu(II) complex to evolve O2, with kCAT=83.2 M−2 s−1. The Cu(II)-hydroperoxide can mediate phenol oxidation, probably through a trigonal bipyramidal ternary transition state based on DFT analysis, favored over catalase activity when low proportion of catalyst is used. In these reactions, structural constraints imposed by the ligand distort the coordination geometry of the metal and controls reactivity.

Published
2022
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28. A Water-Soluble Peptoid Chelator that Can Remove Cu

Author

Anastasia E, Behar, Laurent, Sabater, Maria, Baskin, Christelle, Hureau, and Galia, Maayan

Subjects
Kinetics, Peptoids, Zinc, Amyloid beta-Peptides, Solubility, Alzheimer Disease, Humans, Water, Reactive Oxygen Species, Copper, Chelating Agents
Abstract

Cu bound to amyloid-β (Aβ) peptides can act as a catalyst for the formation of reactive oxygen species (ROS), leading to neuropathologic degradation associated with Alzheimer's disease (AD). An excellent therapeutic approach is to use a chelator that can selectively remove Cu from Cu-Aβ. This chelator should compete with Zn

Published
2021

29. Copper Imbalance in Alzheimer’s Disease and Its Link with the Amyloid Hypothesis: Towards a Combined Clinical, Chemical, and Genetic Etiology

Author

Peter Faller, Anthony R. White, Kasper Planeta Kepp, Alberto Granzotto, Christelle Hureau, Rosanna Squitti, IRCCS Fatebenefratelli - Brescia, Institut de Chimie de Strasbourg, Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of California (UC), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), QIMR Berghofer Medical Research Institute, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Italian Ministry of Health, Alzheimer's Association Part the Cloud: Translational Research Funding for Alzheimer's Disease (PTC) PTC-19-602325 (RS, SLS), European Union’s Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement iMIND—No. 841665, Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UCI), University of California, and Technical University of Denmark [Lyngby] (DTU)

Subjects
Amyloidogenic Proteins, Disease, Neuropathology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Antioxidants, Amyloid beta-Protein Precursor, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Alzheimer Disease, ATP7B, medicine, Humans, Dementia, Amyloid-β, Loss function, Neuroinflammation, Cu, 030304 developmental biology, Aβ, Ions, 0303 health sciences, Chemistry, General Neuroscience, Neurodegeneration, Brain, General Medicine, Metaanalysis, Alzheimer's disease, medicine.disease, Amyloid-β protein precursor, Biochemistry of Alzheimer's disease, Oxidative Stress, Psychiatry and Mental health, Clinical Psychology, Meta-analysis, Metals, Immunology, Wilson's disease, Geriatrics and Gerontology, APP, Copper, 030217 neurology & neurosurgery, Oxidative stress
Abstract

The cause of Alzheimer’s disease (AD) is incompletely defined. To date, no mono-causal treatment has so far reached its primary clinical endpoints, probably due to the complexity and diverse neuropathology contributing to the neurodegenerative process. In the present paper, we describe the plausible etiological role of copper (Cu) imbalance in the disease. Cu imbalance is strongly associated with neurodegeneration in dementia, but a complete biochemical etiology consistent with the clinical, chemical, and genetic data is required to support a causative association, rather than just correlation with disease. We hypothesize that a Cu imbalance in the aging human brain evolves as a gradual shift from bound metal ion pools, associated with both loss of energy production and antioxidant function, to pools of loosely bound metal ions, involved in gain-of-function oxidative stress, a shift that may be aggravated by chemical aging. We explain how this may cause mitochondrial deficits, energy depletion of high-energy demanding neurons, and aggravated protein misfolding/oligomerization to produce different clinical consequences shaped by the severity of risk factors, additional comorbidities, and combinations with other types of pathology. Cu imbalance should be viewed and integrated with concomitant genetic risk factors, aging, metabolic abnormalities, energetic deficits, neuroinflammation, and the relation to tau, prion proteins, α-synuclein, TAR DNA binding protein-43 (TDP-43) as well as systemic comorbidity. Specifically, the Amyloid Hypothesis is strongly intertwined with Cu imbalance because amyloid-β protein precursor (AβPP)/Aβ are probable Cu/Zn binding proteins with a potential role as natural Cu/Zn buffering proteins (loss of function), and via the plausible pathogenic role of Cu-Aβ.

Published
2021
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30. (Bio)chemical Strategies To Modulate Amyloid-β Self-Assembly

Author

Pierre Genevaux, Sara Ayala, Peter Faller, Christelle Hureau, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Physiology, Cognitive Neuroscience, Kinetics, Nanofibers, Plaque, Amyloid, Peptides and proteins, Cleavage (embryo), Fibril, Protein Aggregation, Pathological, Biochemistry, Aggregation, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Amyloid precursor protein, [CHIM]Chemical Sciences, Animals, Humans, Molecule, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Binding selectivity, 030304 developmental biology, 0303 health sciences, Amyloid beta-Peptides, biology, Chemistry, Cell Biology, General Medicine, 3. Good health, Metals, Covalent bond, Oligomers, biology.protein, Biophysics, Chemical chaperone, 030217 neurology & neurosurgery
Abstract

International audience; Amyloid plaques are one of the two hallmarks of Alzheimer’s disease (AD). They consist mainly of fibrils made of self-assembled amyloid-β (Aβ) peptides. Aβ is produced in healthy brains from proteolytic cleavage of the amyloid precursor protein. Aβ aggregates, in particular smaller, soluble aggregates, are toxic to cells. Hence, modulating the self-assembly of Aβ became a very active field of research, with the aim to reduce the amount of the toxic aggregates of Aβ or to block their toxic action. A great variety of molecules, chemical and biological, are able to modify the aggregation of Aβ. Here we give an overview of the different mechanistic ways to modulate Aβ aggregation and on which step in the self-assembly molecules can interfere. We discuss the aggregation modulators according to different important parameters, including the type of interaction (weak interaction, coordination or covalent bonds), the importance of kinetics and thermodynamics, the size of the modulating molecules, and binding specificity.

Published
2019
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31. Biomimetic Cu, Zn and Cu2 complexes inserted in mesoporous silica as catalysts for superoxide dismutation

Author

Gerardo Enrique Camí, Verónica Daier, Eric Rivière, N. Pellegri, Sandra Signorella, Matías Ezequiel Patriarca, Christelle Hureau, Instituto de Química Rosario (IQUIR), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Bioquımicas y Farmaceuticas [Rosario] (FBIOyF), Universidad Nacional de Rosario [Santa Fe]-Universidad Nacional de Rosario [Santa Fe], Universidad Nacional de Rosario [Santa Fe], Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), National University of Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP 0337), Centre National de la Recherche Scientifique (CNRS, PICS 07121), CONICET/CNRS bilateral agreement (Res.991/13), Agency for Science, Technology and Innovation of Santa Fe (ASACTeI, IO 2010-164-16), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
chemistry.chemical_element, 02 engineering and technology, Química Inorgánica y Nuclear, 010402 general chemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, SOD mimics, Propane, Polymer chemistry, Moiety, [CHIM.COOR]Chemical Sciences/Coordination chemistry, General Materials Science, HYBRID MATERIALS, Aqueous solution, Chemistry, SOD MIMICS, Ciencias Químicas, General Chemistry, Mesoporous silica, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Copper, 0104 chemical sciences, Copper/zinc complexes, MESOPOROUS SILICA, Mechanics of Materials, COPPER/ZINC COMPLEXES, Dismutase, Hybrid materials, 0210 nano-technology, Hybrid material, CIENCIAS NATURALES Y EXACTAS
Abstract

Three CuZn-superoxide dismutase (SOD) functional mimics, [CuZn(dien)2(μ-Im)](ClO4)3 (1), [Cu2(dien)2(μ-Im)](ClO4)3 (2) (Im = imidazole, dien = diethylenetriamine), and [CuZn(salpn)Cl2] (3) (H2salpn = 1,3-bis(salicylideneamino)propane), were successfully inserted into the nanochannels of SBA-15 type mesoporous silica with retention of the silica mesostructure. X-ray absorption spectroscopic studies indicate that the encapsulated complexes keep unchanged the first-shell environment of Cu(II) and Zn(II) ions. Magnetic measurements suggest that the nanochannels constrain the geometry of the μ-imidazolate-Cu(II)2 core modifying the relative orientation of the two copper coordination planes. Confinement imposed by the silica nanochannels upon encapsulation of complexes 1 and 2 leads to stable hybrid materials at physiological pH with enhanced SOD activity relative to the free complexes. Unlike the imidazolato-bridged compounds, insertion of 3 in mesoporous silica leads to a less stable hybrid material exhibiting partial release into the aqueous solution and O2•− dismutation rate slower than the free complex. The covalent binding of a mononuclear Cu(dien)Im+ moiety to the mesoporous silica showed lower SOD activity than encapsulated imidazolato-bridged CuZn and Cu2 complexes. The results emphasize the positive effect of encapsulation on SOD activity of imidazolato-bridged dinuclear complexes. Fil: Patriarca, Matías Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Daier, Veronica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Camí, Gerardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Pellegri, Nora Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Rivière, Eric. Université de Paris XI; Francia Fil: Hureau, Christelle. Université de Toulouse; Francia Fil: Signorella, Sandra Rosanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Published
2019
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32. Insights into Second-Sphere Effects on Redox Potentials, Spectroscopic Properties, and Superoxide Dismutase Activity of Manganese Complexes with Schiff-Base Ligands

Author

Christelle Hureau, Joaquín Ferreyra, Fabio Doctorovich, Ana Foi, Micaela Richezzi, Claudia Palopoli, Elodie Anxolabéhère-Mallart, Amandine Conte-Daban, Sandra Signorella, Instituto de Química Rosario (IQUIR), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Bioquımicas y Farmaceuticas [Rosario] (FBIOyF), Universidad Nacional de Rosario [Santa Fe]-Universidad Nacional de Rosario [Santa Fe], Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Departamento de Química Inorgánica, Analítica y Química Física (DQIAQF), Facultad de Ciencias Exactas y Naturales [Buenos Aires] (FCEyN), Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Laboratoire d'Electrochimie Moléculaire (LEM (UMR_7591)), Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), National University of Rosario, Consejo Nacional de Investigaciones Cientifícas y Técnicas (CONICET, PIP 0337), Centre National de la Recherche Scientifique (CNRS, PICS 07121), CONICET/CNRS bilateral agreement (Res. 991/13), Agency for Science, Technology and Innovation of Santa Fe (ASACTeI, IO 2010-164-16), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
General Chemical Engineering, SECOND-SPHERE EFFECTS, chemistry.chemical_element, Manganese, MANGANESE COMPLEXES, Química Inorgánica y Nuclear, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Redox, Article, law.invention, purl.org/becyt/ford/1 [https], lcsh:Chemistry, Superoxide dismutase, Metal, chemistry.chemical_compound, Nucleophile, law, purl.org/becyt/ford/1.4 [https], [CHIM.COOR]Chemical Sciences/Coordination chemistry, Electron paramagnetic resonance, Schiff base, biology, SCHIFF-BASE LIGANDS, 010405 organic chemistry, SOD MIMICS, Ciencias Químicas, General Chemistry, 0104 chemical sciences, lcsh:QD1-999, chemistry, 13. Climate action, visual_art, Nitro, biology.protein, visual_art.visual_art_medium, CIENCIAS NATURALES Y EXACTAS
Abstract

Six Mn-Schiff base complexes, [Mn(X-salpn)]0/+ (salpn = 1,3-bis(sal-ic-ylidenamino)propane, X = H [1], 5-Cl [2], 2,5-F2 [3], 3,5-Cl2 [4], 5-NO2 [5], 3,5-(NO2)2 [6]), were synthesized and characterized in solution, and second-sphere effects on their electrochemical and spectroscopic properties were analyzed. The six complexes catalyze the dismutation of superoxide with catalytic rate constants in the range 0.65 to 1.54 × 106 M–1 s–1 obtained through the nitro blue tetrazolium photoreduction inhibition superoxide dismutases assay, in aqueous medium of pH 7.8. In solution, these compounds possess two labile solvent molecules in the axial positions favoring coordination of the highly nucleophilic O2•– to the metal center. Even complex 5, [Mn(5-(NO2)salpn) (OAc) (H2O)], with an axial acetate in the solid state, behaves as a 1:1 electrolyte in methanolic solution. Electron paramagnetic resonance and UV–vis monitoring of the reaction of [Mn(X-salpn)]0/+ with KO2 demonstrates that in diluted solutions these complexes behave as catalysts supporting several additions of excess O2•–, but at high complex concentrations (≥0.75 mM) catalyst self-inhibition occurs by the formation of a catalytically inactive dimer. The correlation of spectroscopic, electrochemical, and kinetics data suggest that second-sphere effects control the oxidation states of Mn involved in the O2•– dismutation cycle catalyzed by complexes 1–6 and modulate the strength of the Mn-substrate adduct for electron-transfer through an inner-sphere mechanism. Fil: Palopoli, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Ferreyra, Joaquín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Conte Daban, Amandine. Université Paul Sabatier; Francia. Centre National de la Recherche Scientifique; Francia Fil: Richezzi, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Foi, Maria Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Anxolabéhère, Elodie. Centre National de la Recherche Scientifique; Francia. Université Paris Diderot - Paris 7; Francia Fil: Hureau, Christelle. Université Paul Sabatier; Francia Fil: Signorella, Sandra Rosanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Published
2019
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33. Solid-state and solution characterizations of [(TMPA)Cu(II)(SO

Author

Léonie, Berthonnaud, Charlène, Esmieu, Sonia, Mallet-Ladeira, and Christelle, Hureau

Subjects
Coordination Complexes, Thiosulfates, Sulfites, Colorimetry, Food Contamination, Copper, Chelating Agents
Abstract

Sulfite (SO

Published
2021

34. Measurement of Interpeptidic CuII Exchange Rate Constants of CuII -Amyloid-β Complexes to Small Peptide Motifs by Tryptophan Fluorescence Quenching

Author

Charlène Esmieu, Cheryle N Beuning, Pierre Dorlet, Luca J. Zocchi, Debbie C. Crans, Kyangwi P. Malikidogo, Christelle Hureau, Department of Chemistry, Colorado State University, Colorado State University [Fort Collins] (CSU), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Microbiologie de la Méditerranée (IMM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), ACS Petroleum Research Fund through grant 55242-ND6, European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
chemistry.chemical_classification, Quenching (fluorescence), Synaptic cleft, 010405 organic chemistry, Ligand, Tryptophan, Peptide, Peptides and proteins, 010402 general chemistry, 01 natural sciences, Amides, Fluorescence, 0104 chemical sciences, Inorganic Chemistry, chemistry.chemical_compound, Crystallography, Reaction rate constant, chemistry, Amide, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Kinetic parameters, Physical and Theoretical Chemistry, Histidine, Electron paramagnetic resonance spectroscopy
Abstract

International audience; The interpeptidic CuII exchange rate constants were measured for two Cu amyloid-β complexes, Cu(Aβ1–16) and Cu(Aβ1–28), to fluorescent peptides GHW and DAHW using a quantitative tryptophan fluorescence quenching methodology. The second-order rate constants were determined at three pH values (6.8, 7.4, and 8.7) important to the two Cu(Aβ) coordination complexes, components Cu(Aβ)I and Cu(Aβ)II. The interpeptidic CuII exchange rate constant is approximately 104 M–1 s–1 but varies in magnitude depending on many variables. These include pH, length of the Aβ peptide, location of the anchoring histidine ligand in the fluorescent peptide, number of amide deprotonations required in the tryptophan peptide to coordinate CuII, and interconversion between Cu(Aβ)I and Cu(Aβ)II. We also present EPR data probing the CuII exchange between peptides and the formation of ternary species between Cu(Aβ) and GHW. As the nonfluorescent GHK and DAHK peptides are important motifs found in the blood and serum, their ability to sequester CuII ions from Cu(Aβ) complexes may be relevant for the metal homeostasis and its implication in Alzheimer’s disease. Thus, their kinetic CuII interpeptidic exchange rate constants are important chemical rate constants that can help elucidate the complex CuII trafficking puzzle in the synaptic cleft.

Published
2021
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35. Measurement of Interpeptidic Cu

Author

Cheryle N, Beuning, Luca J, Zocchi, Kyangwi P, Malikidogo, Charlène, Esmieu, Pierre, Dorlet, Debbie C, Crans, and Christelle, Hureau

Subjects
Amyloid beta-Peptides, Electron Spin Resonance Spectroscopy, Molecular Conformation, Tryptophan, Fluorometry, Spectrophotometry, Ultraviolet, Peptides, Copper, Fluorescence
Abstract

The interpeptidic Cu

Published
2021

36. Synthesis, characterization, and biological activity of novel 3 d metal coordination compounds with 2‐acetylpyridine N 4 ‐allyl‐ S ‐methylisothiosemicarbazone

Author

Victor Ch. Kravtsov, Aurelian Gulea, Pavlina Bourosh, Olga Garbuz, Christelle Hureau, Irina Usataia, and Vasilii Graur

Subjects
chemistry.chemical_classification, 010405 organic chemistry, Biological activity, General Chemistry, Crystal structure, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, 0104 chemical sciences, Characterization (materials science), Coordination complex, Inorganic Chemistry, Metal, chemistry.chemical_compound, chemistry, visual_art, visual_art.visual_art_medium, 2-Acetylpyridine
Published
2021
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37. Unexpected Trends in Copper Removal from Aβ Peptide: When Less Ligand Is Better and Zn Helps

Author

Charlène Esmieu, Amandine Conte-Daban, Olga Iranzo, Raúl Balderrama-Martínez-Sotomayor, Christelle Hureau, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CONACYT (grant 439618), PRESTIGE Programm (grant n. PCOFUND-GA-2013−609102), European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Phenanthroline, Molecular Conformation, Peptide, Free radicals, Peptides and proteins, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, medicine.disease_cause, Ligands, 01 natural sciences, Redox, Inorganic Chemistry, chemistry.chemical_compound, Coordination Complexes, medicine, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Physical and Theoretical Chemistry, Binding site, Redox reactions, chemistry.chemical_classification, Reactive oxygen species, Amyloid beta-Peptides, 010405 organic chemistry, Ligand, Chemistry, Rational design, 0104 chemical sciences, Oxidative Stress, Zinc, Mixtures, Biophysics, Reactive Oxygen Species, Oxidation-Reduction, Oxidative stress, Copper, Phenanthrolines
Abstract

International audience; Cu, Zn, and amyloid-β (Aβ) peptides play an important role in the etiology of Alzheimer’s disease (AD). Their interaction indeed modifies the self-assembly propensity of the peptide that is at the origin of the deposition of insoluble peptide aggregates in the amyloid plaque, a hallmark found in AD brains. Another even more important fallout of the Cu binding to Aβ peptide is the formation of reactive oxygen species (ROS) that contributes to the overall oxidative stress detected in the disease and is due to the redox ability of the Cu ions. Many therapeutic approaches are currently developed to aid fighting against AD, one of them targeting the redox-active Cu ions. Along this research line, we report in the present article the use of a phenanthroline-based peptide-like ligand (L), which is able to withdraw Cu from Aβ and redox-silence it in a very stable 4N Cu(II) binding site even in the presence of Zn(II). In addition and in contrast to what is usually observed, the presence of excess of L lessens the searched effect of ROS production prevention, but it is counterbalanced by the co-presence of Zn(II). To explain such unprecedented trends, we proposed a mechanism that involves the redox reaction between Cu(II)L and Cu(I)L2. We thus illustrated (i) how speciation and redox chemistry can weaken the effect of a ligand that would have appeared perfectly suitable if only tested in a 1:1 ratio and on CuAβ and (ii) how Zn overcomes the undesired lessening of ROS arrest due to excess of ligand. In brief, we have shown how working in biologically relevant conditions is important for the understanding of all of the reactions at play and this must be taken into consideration for the further rational design of ligands aiming to become drug candidates.

Published
2021
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39. Concentration‐Dependent Interactions of Amphiphilic PiB Derivative Metal Complexes with Amyloid Peptides Aβ and Amylin**

Author

Sara Lacerda, Éva Tóth, Carlos F. G. C. Geraldes, Inga Relich, Christelle Hureau, Jean-François Morfin, Zoltán Garda, Agnès Pallier, Alexandre C. Oliveira, Saida Majdoub, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Faculty of Science and Technology, University of Debrecen, University of Coimbra [Portugal] (UC), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), French National Research Agency (grant DIVA ANR-16-CE18-0022-01), Fundaçao para a Ciencia e a Tecnologia (FCT), Portugal (programmes UIDB/00313/2020 and UIDP/00313/2020), FEDER/COMPETE 2020-EU, European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE18-0022,DIVA,Visualization de l'amylin avec des sondes métalliques pour une imagerie du diabète(2016), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Jakab Toth, Eva, and Alzheimer's disease and Zinc: the missing link ? - aLzINK - - H20202015-03-01 - 2020-02-29 - 638712 - VALID

Subjects
Biodistribution, Amyloid, [SDV]Life Sciences [q-bio], Amylin, Peptide, 010402 general chemistry, 01 natural sciences, Catalysis, Mice, Alzheimer Disease, Coordination Complexes, [CHIM] Chemical Sciences, Amphiphile, Animals, [CHIM]Chemical Sciences, Tissue Distribution, Surface plasmon resonance, Amylin binding, chemistry.chemical_classification, Amyloid beta-Peptides, 010405 organic chemistry, Chemistry, Organic Chemistry, General Chemistry, Peptide Fragments, 0104 chemical sciences, Islet Amyloid Polypeptide, [SDV] Life Sciences [q-bio], Biophysics, Linker
Abstract

International audience; Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents. The attachment of a metal complex to amyloid recognition units typically leads to a decrease in peptide affinity. We show here that by separating a macrocyclic GdL chelate and a PiB targeting unit with a long hydrophobic C10 linker, it is possible to attain nanomolar affinities for both Aβ 1‐40 ( K d = 4.4 nM) and amylin ( K d = 4.5 nM), implicated respectively in Alzheimer’s disease and diabetes. The Scatchard analysis of surface plasmon resonance data obtained for a series of amphiphilic, PiB derivative GdL complexes indicate that their Aβ 1‐40 or amylin binding affinity varies with their concentration, thus micellar aggregation state. The GdL chelates also affect peptide aggregation kinetics, as probed by thioflavin‐T fluorescence assays. A 2D NMR study allowed identifying that the hydrophilic region of Aβ 1‐40 is involved in the interaction between the monomer peptide and the Gd 3+ complex. Finally, ex vivo biodistribution experiments were conducted in healthy mice by using 111 In labelled analogues. Their pancreatic uptake, ~3%ID/g, is promising to envisage amylin imaging in diabetic animals.

Published
2021
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40. A Water‐Soluble Peptoid Chelator that Can Remove Cu 2+ from Amyloid‐β Peptides and Stop the Formation of Reactive Oxygen Species Associated with Alzheimer's Disease

Author

Maria Baskin, Galia Maayan, Laurent Sabater, Anastasia E Behar, Christelle Hureau, Technion - Israel Institute of Technology [Haifa], Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Israel Science Foundation (ISF) grant number 395/16, European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Synaptic cleft, Peptidomimetic, chemistry.chemical_element, Peptide, Context (language use), Zinc, 010402 general chemistry, 01 natural sciences, Catalysis, 03 medical and health sciences, chemistry.chemical_compound, Peptoids, Amyloids, Zn, Chelation, [CHIM.COOR]Chemical Sciences/Coordination chemistry, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, 010405 organic chemistry, Peptoid, General Medicine, General Chemistry, Alzheimer's disease, Combinatorial chemistry, 0104 chemical sciences, Cu chelators, chemistry, Peptides
Abstract

Cu bound to amyloid-β (Aβ) peptides can act as a catalyst for the formation of reactive oxygen species (ROS), leading to neuropathologic degradation associated with Alzheimer's disease (AD). An excellent therapeutic approach is to use a chelator that can selectively remove Cu from Cu-Aβ. This chelator should compete with Zn2+ ions (Zn) that are present in the synaptic cleft while forming a nontoxic Cu complex. Herein we describe P3, a water-soluble peptidomimetic chelator that selectively removes Cu2+ from Cu-Aβ in the presence of Zn and prevent the formation of ROS even in a reductive environment. We demonstrate, based on extensive spectroscopic analysis, that although P3 extracts Zn from Cu,Zn-Aβ faster than it removes Cu, the formed Zn complexes are kinetic products that further dissociate, while CuP3 is formed as an exclusive stable thermodynamic product. Our unique findings, combined with the bioavailability of peptoids, make P3 an excellent drug candidate in the context of AD.

Published
2021
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41. Impact of N-Truncated Aβ Peptides on Cu- and Cu(Aβ)-Generated ROS: CuI Matters!

Author

Charlène Esmieu, Christelle Hureau, Guillaume Ferrand, Valentina Borghesani, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), PRESTIGE Programm (grant no. PCOFUND-GA-2013–609102), European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées

Subjects
Gene isoform, Stereochemistry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, chemistry.chemical_element, Peptide, 010402 general chemistry, 01 natural sciences, Catalysis, Bioinorganic chemistry, Chelation, [CHIM.COOR]Chemical Sciences/Coordination chemistry, chemistry.chemical_classification, Reactive oxygen species, 010405 organic chemistry, Chemistry, Organic Chemistry, Amyloid beta-peptides, General Chemistry, Affinities, Copper, In vitro, 0104 chemical sciences, Chelates
Abstract

International audience; In vitro Cu(Aβ1–x)-induced ROS production has been extensively studied. Conversely, the ability of N-truncated isoforms of Aβ to alter the Cu-induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N-Truncated peptides at the positions 4 and 11 (Aβ4–x and Aβ11–x) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for CuII compared to the Aβ1–x peptide. It has further been proposed that the role of Aβ4–x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII, CuI coordination is expected to be the same for N-truncated and N-intact peptides. Herein, we report in-depth characterizations and ROS production studies of Cu (CuI and CuII) complexes of the Aβ4–16 and Aβ11–16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when CuI is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aβ1–16), the N-truncated peptides are not able to fully preclude Cu(Aβ1–16)-induced ROS production.

Published
2021
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42. Effect of coordination dissymmetry on the catalytic activity of manganese catalase mimics

Author

Ripul Mehrotra, Christelle Hureau, Sandra Signorella, Claudia Palopoli, Micaela Richezzi, Instituto de Química Rosario (IQUIR), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Bioquımicas y Farmaceuticas [Rosario] (FBIOyF), Universidad Nacional de Rosario [Santa Fe]-Universidad Nacional de Rosario [Santa Fe], Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), National University of Rosario (PIPBIO553), Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET, PIP 0337 and PUE 0068), Centre National de la Recherche Scientifique (CNRS, PICS 07121), Agency for Science, Technology and Innovation of Santa Fe (ASACTeI, IO 2010-164-16), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Carboxylic Acids, Ligands, 010402 general chemistry, 01 natural sciences, Biochemistry, Medicinal chemistry, Catalysis, Adduct, Inorganic Chemistry, chemistry.chemical_compound, Coordination Complexes, CAT activity, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Enzyme kinetics, Carboxylate, Unsymmetrical ligands, Spectroscopy, Manganese, 010405 organic chemistry, Ligand, Spectrum Analysis, Biomimics, Molecular Mimicry, Hydrogen Peroxide, Catalase, Manganese Catalase, Decomposition, 0104 chemical sciences, Solvent, Kinetics, chemistry, diMn complexes, Nitrogen Oxides, Mechanism, Oxidation-Reduction
Abstract

International audience; Two mixed-valence Mn(II)Mn(III) complexes, [Mn2L1(OAc)2(H2O)]BPh4·2.5H2O and [Mn2L2(OAc)2]·4H2O, obtained with unsymmetrical N4O2-hexadentate L1(2−) (H2L1 = 2-(N,N-bis(2-(pyridylmethyl)aminomethyl)-6-(N-(2-hydroxybenzyl)benzylaminomethyl)-4-methylphenol) and N4O3-heptadentate L2(3−) (NaH2L2 = 2-(N,N-bis(2-(pyridylmethyl)aminomethyl)-6-(N′-(2-hydroxybenzyl)(carboxymethyl)aminomethyl)-4-methylphenol sodium salt) ligands, have been prepared and characterized. Both complexes share a μ-phenolate-bis(μ-acetate)Mn(II)Mn(III) core and N3O3-coordination sphere around the Mn(II) ion, but differ in the donor groups surrounding Mn(III) (NO4(solvent) and NO5). In non-protic solvents, these two complexes are able to disproportionate at least 3600 equiv. of H2O2 without significant decomposition, with first-order dependence on catalyst and saturation kinetics on [H2O2]. Spectroscopic monitoring of the reaction mixtures revealed the two complexes disproportionate H2O2 employing a different redox cycle, with retention of dinuclearity. The higher catalytic efficiency of [Mn2L2(OAc)2] was rationalized in terms of the larger labilizing effect of the heptadentate ligand that favors the acetate-shift and the replacement of the non-coordinating benzyl arm of L1 by a carboxylate arm in L2 which facilitates the formation of the catalyst-H2O2 adduct, placing [Mn2L2(OAc)2] as the most efficient among the phenolate-bridged diMn catalysts based on the kcat/KM criterion.

Published
2020
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43. The Aggregation Pattern of Aβ

Author

Ewelina, Stefaniak, Elena, Atrian-Blasco, Wojciech, Goch, Laurent, Sabater, Christelle, Hureau, and Wojciech, Bal

Abstract

Alzheimer's disease (AD) is one of the most common of the multifactorial diseases and is characterized by a range of abnormal molecular processes, such as the accumulation of extracellular plaques containing the amyloid-β (Aβ) peptides and dyshomeostasis of copper in the brain. In this study, we have investigated the effect of Cu

Published
2020

45. Preparation, characterization and activity of CuZn and Cu

Author

Matías, Patriarca, Verónica, Daier, Gerardo, Camí, Eric, Rivière, Christelle, Hureau, and Sandra, Signorella

Subjects
Zinc, Superoxide Dismutase, Electron Spin Resonance Spectroscopy, Imidazoles, Organometallic Compounds, Spectrophotometry, Ultraviolet, Silicon Dioxide, Catalysis, Copper
Abstract

Encapsulation of three superoxide dismutase (SOD) functional mimics, [CuZn(dien)

Published
2020

46. An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase

Author

Anne-Sophie Bernard, Philippe Pelupessy, Koudedja Coulibaly, Elodie Quévrain, Christelle Hureau, Nicolas Delsuc, Katalin Selmeczi, Ágnes Dancs, Elodie Tauziet, Amandine Vincent, Jennifer Rodon Fores, Philippe Seksik, Amandine Conte-Daban, Clotilde Policar, Peptides, glycoconjugués et métaux en biologie (LBM-E1), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire Lorrain de Chimie Moléculaire (L2CM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Structure et Dynamique des Biomolécules (LBM-E3), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-05-GANI-0001,GenOvul,Exploitation de la variabilité génétique intra et inter-espèces pour l'étude du déterminisme génétique du taux d'ovulation(2005), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), delsuc, nicolas, Réseau de Génomique des animaux d'élevage GENANIMAL - Exploitation de la variabilité génétique intra et inter-espèces pour l'étude du déterminisme génétique du taux d'ovulation - - GenOvul2005 - ANR-05-GANI-0001 - GANI - VALID, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Lipopolysaccharides, Antioxidant, Intrinsic activity, Colon, medicine.medical_treatment, Copper metabolism, Biocompatible Materials, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Redox, Catalysis, Superoxide dismutase, [CHIM] Chemical Sciences, Materials Chemistry, medicine, Humans, [CHIM]Chemical Sciences, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Amino Acid Sequence, Peptide sequence, Copper complex, biology, Superoxide Dismutase, 010405 organic chemistry, Chemistry, Interleukin-8, Metals and Alloys, General Chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Oxidative Stress, Biochemistry, Ceramics and Composites, biology.protein, Peptides, HT29 Cells, Copper, Oxidative stress
Abstract

International audience; A combinatorial approach using a One-Bead-One-Compound method and a screening based on an SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effect when cells were submitted to oxidative stress.

Published
2020
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48. Mutations of Histidine 13 to Arginine and Arginine 5 to Glycine Are Responsible for Different Coordination Sites of Zinc(II) to Human and Murine Peptides

Author

Peter Faller, Sabrina Noël, Denis Testemale, Valentina Borghesani, Emmanuel Guillon, Bruno Alies, Christelle Hureau, Stéphanie Sayen, ChemBioPharm, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Moléculaire de Reims - UMR 7312 (ICMR), SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Matériaux, Rayonnements, Structure (MRS), Institut Néel (NEEL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), European Synchrotron Radiation Facility (ESRF), Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), European Project: 638712,H2020,ERC-2014-STG,aLzINK(2015), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Matériaux, Rayonnements, Structure (NEEL - MRS), and Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Arginine, Glycine, Mutagenesis (molecular biology technique), chemistry.chemical_element, Peptide, Zinc, 010402 general chemistry, 01 natural sciences, Catalysis, Mice, Alzheimer Disease, Coordination Complexes, [CHIM]Chemical Sciences, Animals, Humans, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Histidine, Binding site, Nuclear Magnetic Resonance, Biomolecular, chemistry.chemical_classification, Amyloid beta-Peptides, Binding Sites, 010405 organic chemistry, Organic Chemistry, Bioinorganic chemistry, General Chemistry, Hydrogen-Ion Concentration, 0104 chemical sciences, X-Ray Absorption Spectroscopy, chemistry, Biochemistry, Mutagenesis, Site-Directed, Copper
Abstract

International audience; Because mice and rats do not naturally develop Alzheimer's disease, genetically modified animals are required to study this pathology. This striking difference in terms of disease onset could be due to three alterations in the murine sequence (R5G, Y10F and H13R) of the amyloid‐β peptide with respect to the human counterpart. Whether the metal‐ion binding properties of the murine peptide are at the origin of such different amyloidogenicity of the two peptides is still an open question. Herein, the main zinc binding site to the murine amyloid‐β at physiological pH has been determined through the combination of several spectroscopic and analytical methods applied to a series of six peptides with one or two of the key mutations. These results have been compared with the zinc binding site encountered in the human peptide. A coordination mechanism that demonstrates the importance of the H13R and R5G mutations in the different zinc environments present in the murine and human peptides is proposed. The nature of the minor zinc species present at physiological pH is also suggested for both peptides. Finally, the biological relevance and fallouts of the differences determined in zinc binding to human versus murine amyloid‐β are also discussed.

Published
2018
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49. N4-Tetradentate Chelators Efficiently Regulate Copper Homeostasis and Prevent ROS Production Induced by Copper-Amyloid-β1-16

Author

Bernard Meunier, Weixin Zhang, Anne Robert, Yan Liu, and Christelle Hureau

Subjects
Coordination sphere, 010405 organic chemistry, Chemistry, Organic Chemistry, chemistry.chemical_element, General Chemistry, Zinc, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Copper, Catalysis, In vitro, 0104 chemical sciences, Metal, Aminoquinoline, visual_art, Biophysics, visual_art.visual_art_medium, medicine, Selectivity, Oxidative stress, medicine.drug
Abstract

The disruption of copper homeostasis and the oxidative stress induced by Cu-amyloids are crucial features of Alzheimer's disease pathology. The copper specific N4 -tetradendate ligands TDMQ20 and 1 are able to fully inhibit in vitro the aerobic oxidation of ascorbate induced by Cu-Aβ1-16 , even in the presence of 100 molar equivalents of ZnII with respect to CuII , whereas other ligands with N2 O2 or N3 O2 coordination spheres failed to do so. This essential result indicates that, in addition to metal selectivity, the coordination sphere of copper chelators should exhibit a N4 -tetradendate motif to be able to reduce an oxidative stress in the zinc-rich physiological environment of brain. The N4 -scaffolds of these two aminoquinoline-based ligands, TDMQ20 or 1, suitable for a square-planar coordination of copper(II), allowed them to enhance both the selectivity for copper and the ability to reduce the oxidative stress induced by copper-amyloid in a zinc-rich environment.

Published
2018
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50. Measurement of Interpeptidic Cu(II) Exchange Rate Constants by Static Fluorescence Quenching of Tryptophan

Author

Debbie C. Crans, Béatrice Mestre-Voegtlé, Cheryle N Beuning, Christelle Hureau, Peter Faller, Department of Chemistry, Colorado State University, Colorado State University [Fort Collins] (CSU), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Chimie de Strasbourg, and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
010405 organic chemistry, Chemistry, Lysine, Molecular Conformation, Tryptophan, 010402 general chemistry, Mass spectrometry, Kinetic energy, 01 natural sciences, Fluorescence, Molecular conformation, 0104 chemical sciences, Inorganic Chemistry, Residue (chemistry), Spectrometry, Fluorescence, Reaction rate constant, Organometallic Compounds, Physical chemistry, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Physical and Theoretical Chemistry, Peptides, Copper
Abstract

International audience; The interpeptidic exchange of Cu(II) between biologically relevant peptides like Gly-His-Lys (GHK) was measured through proximity static fluorescence quenching of a noncoordinating tryptophan residue by Cu(II). The inability to spectrally distinguish between starting and final Cu(H–1GHK)+ complexes by the current methods was solved by the replacement of noncoordinating lysine for tryptophan in the starting complex, Cu(H–1GHW). Because the apoGHW is the only fluorescent species, the recovered fluorescence is directly proportional to the [Cu(II)]exchanged between GHW and GHK. The apparent second-order rate constants of the exchanges from Cu(H–1GHW) to GHK and DAHK are 1.6 (±0.2) × 102 and 5.0 (±0.7) × 101 M–1 s–1, respectively. The easy-to-implement kinetic fluorescent method described here for Cu(II) interpeptidic exchange can be expanded to other biological systems.

Published
2018
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