7 results on '"Proux O"'
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2. A Series of Ni Complexes Based on a Versatile ATCUN-Like Tripeptide Scaffold to Decipher Key Parameters for Superoxide Dismutase Activity.
- Author
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Domergue J, Guinard P, Douillard M, Pécaut J, Hostachy S, Proux O, Lebrun C, Le Goff A, Maldivi P, Duboc C, and Delangle P
- Subjects
- Reactive Oxygen Species, Oxidation-Reduction, Superoxides chemistry, Nickel chemistry, Hydrogen Peroxide chemistry, Superoxide Dismutase chemistry
- Abstract
The cellular level of reactive oxygen species (ROS) has to be controlled to avoid some pathologies, especially those linked to oxidative stress. One strategy for designing antioxidants consists of modeling natural enzymes involved in ROS degradation. Among them, nickel superoxide dismutase (NiSOD) catalyzes the dismutation of the superoxide radical anion, O
2 , into O•- , into O2 O2 O2 . We report here Ni complexes with tripeptides derived from the amino-terminal CuII - and NiII -binding (ATCUN) motif that mimics some structural features found in the active site of the NiSOD. A series of six mononuclear NiII complexes were investigated in water at physiological pH with different first coordination spheres, from compounds with a N3S to N2S2 set, and also complexes that are in equilibrium between the N -coordination (N3S) and S -coordination (N2S2). They were fully characterized by a combination of spectroscopic techniques, including1 H NMR, UV-vis, circular dichroism, and X-ray absorption spectroscopy, together with theoretical calculations and their redox properties studied by cyclic voltammetry. They all display SOD-like activity, with a kcat ranging between 0.5 and 2.0 × 106 M-1 s-1 . The complexes in which the two coordination modes are in equilibrium are the most efficient, suggesting a beneficial effect of a nearby proton relay.- Published
- 2023
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3. Elucidation of Metal-Sugar Complexes: When Tungstate Combines with d-Mannose.
- Author
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El Mohammad S, Proux O, Aguilar A, Hazemann JL, Legens C, Chizallet C, and Larmier K
- Abstract
The control of metal-sugar complexes speciation in solution is crucial in an energy transition context. Herein, the formation of tungstate-mannose complexes is unraveled in aqueous solution using a multitechnique experimental and theoretical approach.
13 C nuclear magnetic resonance (NMR), as well as13 C-1 H and1 H-1 H correlation spectra, analyzed in the light of coordination-induced shift method and conformation analysis, were employed to characterize the structure of the sugar involved in the complexes. X-ray absorption near edge structure spectroscopy was performed to provide relevant information about the metal electronic and coordination environment. The calculation of13 C NMR chemical shifts for a series of tungstate-mannose complexes using density functional theory (DFT) is a key to identify the appropriate structure among several candidates. Furthermore, a parametric study based on several relevant parameters, namely, pH and tungstate concentration, was carried out to look over the change of the nature and concentrations of the complexes. Two series of complexes were detected, in which the metallic core is either in a ditungstate or a monotungstate form. With respect to previous proposals, we identify two new species. Dinuclear complexes involve both α- and β-furanose forms chelating the metallic center in a tetradentate fashion. A hydrate form chelating a ditungstate core is also revealed. One monotungstate complex appears at high pH, in which a tetrahedral tungstate center is bound to α-mannofuranose through a monodentate site at the second deprotonated hydroxyl group. This unequalled level of knowledge opens the door to structure-reactivity relationships.- Published
- 2023
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4. A Bioinspired Ni II Superoxide Dismutase Catalyst Designed on an ATCUN-like Binding Motif.
- Author
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Domergue J, Guinard P, Douillard M, Pécaut J, Proux O, Lebrun C, Le Goff A, Maldivi P, Delangle P, and Duboc C
- Subjects
- Catalysis, Density Functional Theory, Models, Chemical, Molecular Structure, Nickel chemistry, Superoxide Dismutase chemistry, Biomimetic Materials chemistry, Coordination Complexes chemistry, Superoxides chemistry
- Abstract
Nickel superoxide dismutase (NiSOD) is an enzyme that protects cells against O
2 · - . While the structure of its active site is known, the mechanism of the catalytic cycle is still not elucidated. Its active site displays a square planar NiII center with two thiolates, the terminal amine and an amidate. We report here a bioinspired NiII complex built on an ATCUN-like binding motif modulated with one cysteine, which demonstrates catalytic SOD activity in water ( kcat at pH = 8.1). Its reactivity with O5 was also studied in acetonitrile allowing trapping two different short-lived species that were characterized by electron paramagnetic resonance or spectroelectrochemistry and a combination of density functional theory (DFT) and time-dependent DFT calculations. Based on these observations, we propose that O-1 s-1 O2 · - was also studied in acetonitrile allowing trapping two different short-lived species that were characterized by electron paramagnetic resonance or spectroelectrochemistry and a combination of density functional theory (DFT) and time-dependent DFT calculations. Based on these observations, we propose that O2 · - interacts first with the complex outer sphere through a H-bond with the peptide scaffold in a [NiII O2 · - ] species. This first species could then evolve into a NiIII hydroperoxo inner sphere species through a reaction driven by protonation that is thermodynamically highly favored according to DFT calculations.- Published
- 2021
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5. Mononuclear Ni(II) Complexes with a S3O Coordination Sphere Based on a Tripodal Cysteine-Rich Ligand: pH Tuning of the Superoxide Dismutase Activity.
- Author
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Domergue J, Pécaut J, Proux O, Lebrun C, Gateau C, Le Goff A, Maldivi P, Duboc C, and Delangle P
- Subjects
- Biomimetic Materials chemistry, Hydrogen-Ion Concentration, Ligands, Oxidation-Reduction, Coordination Complexes chemistry, Cysteine chemistry, Nickel chemistry, Sulfur Compounds chemistry, Superoxide Dismutase chemistry
- Abstract
The superoxide dismutase (SOD) activity of mononuclear Ni
II complexes, whose structures are inspired by the NiSOD, has been investigated. They have been designed with a sulfur-rich pseudopeptide ligand, derived from nitrilotriacetic acid (NTA), where the three acid functions are grafted with cysteines ( L3S ). Two mononuclear complexes, which exist in pH-dependent proportions, have been fully characterized by a combination of spectroscopic techniques including1 H NMR, UV-vis, circular dichroism, and X-ray absorption spectroscopy, together with theoretical calculations. They display similar square-planar S3O coordination, with the three thiolates of the three cysteine moieties from L3S coordinated to the NiII ion, together with either a water molecule at physiological pH, as [Ni L3S (OH2 )]- , or a hydroxo ion in more basic conditions, as [Ni L3S (OH)]2- . The1 H NMR study has revealed that contrary to the hydroxo ligand, the bound water molecule is labile. The cyclic voltammogram of both complexes displays an irreversible one-electron oxidation process assigned to the NiII /NiIII redox system with Epa = 0.48 and 0.31 V versus SCE for Ni L3S (OH2 ) and Ni L3S (OH), respectively. The SOD activity of both complexes has been tested. On the basis of the xanthine oxidase assay, an IC50 of about 1 μM has been measured at pH 7.4, where Ni L3S (OH2 ) is mainly present (93% of the NiII species), while the IC50 is larger than 100 μM at pH 9.6, where Ni L3S (OH) is the major species (92% of the NiII species). Interestingly, only Ni L3S (OH2 ) displays SOD activity, suggesting that the presence of a labile ligand is required. The SOD activity has been also evaluated under catalytic conditions at pH 7.75, where the ratio between Ni L3S (OH2 )/ Ni L3S (OH) is about (86:14), and a rate constant, kcat = 1.8 × 105 M-1 s-1 , has been measured. Ni L3S (OH2 ) is thus the first low-molecular weight, synthetic, bioinspired Ni complex that displays catalytic SOD activity in water at physiological pH, although it does not contain any N-donor ligand in its first coordination sphere, as in the NiSOD. Overall, the data show that a key structural feature is the presence of a labile ligand in the coordination sphere of the NiII ion.- Published
- 2019
- Full Text
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6. Mercury Trithiolate Binding (HgS 3 ) to a de Novo Designed Cyclic Decapeptide with Three Preoriented Cysteine Side Chains.
- Author
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Sénèque O, Rousselot-Pailley P, Pujol A, Boturyn D, Crouzy S, Proux O, Manceau A, Lebrun C, and Delangle P
- Abstract
Mercury(II) is an unphysiological soft ion with high binding affinity for thiolate ligands. Its toxicity lies in the interactions with low molecular weight thiols including glutathione and cysteine-containing proteins that disrupt the thiol balance and alter vital functions. However, mercury can also be detoxified via interactions with Hg(II)-responsive regulatory proteins such as MerR, which coordinates Hg(II) with three cysteine residues in a trigonal planar fashion (HgS
3 coordination). The model cyclodecapeptide P3C , c(GCTCSGCSRP) was designed to promote Hg(II) chelation in a HgS3 coordination environment through the parallel orientation of three cysteine side chains. The binding motif is derived from the dicysteine P2C cyclodecapeptide validated previously as a model for d10 metal transporters containing the binding sequence CxxC. The formation of the mononuclear HgP3C complex with a HgS3 coordination is demonstrated using electrospray ionization mass spectrometry, UV absorption, and199 Hg NMR. Hg LIII -edge extended X-ray absorption fine structure (EXAFS) spectroscopy indicates that the Hg(II) coordination environment is T-shaped with two short Hg-S distances at 2.45 Å and one longer distance at 2.60 Å. The solution structure of the HgP3C complex was refined based on1 H-1 H NMR constraints and EXAFS results. The cyclic peptide scaffold has a rectangular shape with the three binding cysteine side chains pointing toward Hg(II). The HgP3C H complex has a p Ka of 4.3, indicating that the HgS3 coordination mode is stable over a large range of pH. This low p Ka value suggests that the preorientation of the three cysteine groups is particularly well-achieved for Hg(II) trithiolate coordination in P3C .- Published
- 2018
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7. Reactivity of Cys4 zinc finger domains with gold(III) complexes: insights into the formation of "gold fingers".
- Author
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Jacques A, Lebrun C, Casini A, Kieffer I, Proux O, Latour JM, and Sénèque O
- Subjects
- Humans, Molecular Structure, Organogold Compounds chemistry, Zinc Fingers
- Abstract
Gold(I) complexes such as auranofin or aurothiomalate have been used as therapeutic agents for the treatment of rheumatoid arthritis for several decades. Several gold(I) and gold(III) complexes have also shown in vitro anticancer properties against human cancer cell lines, including cell lines resistant to cisplatin. Because of the thiophilicity of gold, cysteine-containing proteins appear as likely targets for gold complexes. Among them, zinc finger proteins have attracted attention and, recently, gold(I) and gold(III) complexes have been shown to inhibit poly(adenosine diphosphate ribose)polymerase-1 (PARP-1), which is an essential protein involved in DNA repair and in cancer resistance to chemotherapies. In this Article, we characterize the reactivity of the gold(III) complex [Au(III)(terpy)Cl]Cl2 (Auterpy) with a model of Zn(Cys)4 "zinc ribbon" zinc finger by a combination of absorption spectroscopy, circular dichroism, mass spectrometry, high-performance liquid chromatography analysis, and X-ray absorption spectroscopy. We show that the Zn(Cys)4 site of Zn·LZR is rapidly oxidized by Auterpy to form a disulfide bond. The Zn(2+) ion is released, and the two remaining cysteines coordinate the Au(+) ion that is produced during the redox reaction. Subsequent oxidation of these cysteines can take place in conditions of excess gold(III) complex. In the presence of excess free thiols mimicking the presence of glutathione in cells, mixing of the zinc finger model and gold(III) complex yields a different product: complex (Au(I))2·LZR with two Au(+) ions bound to cysteines is formed. Thus, on the basis of detailed speciation and kinetic measurements, we demonstrate herein that the destruction of Zn(Cys)4 zinc fingers by gold(III) complexes to achieve the formation of "gold fingers" is worth consideration, either directly or mediated by reducing agents.
- Published
- 2015
- Full Text
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