A Trishistidine Pseudopeptide with Ability to Remove Both Cu Ι and Cu ΙΙ from the Amyloid-β Peptide and to Stop the Associated ROS Formation

Abstract : The pseudopeptide L, derived from a nitrilotriacetic acid scaffold and functionalized with three histidine moieties, is reminiscent of the amino acid side chains encountered in the Alzheimer's peptide (Aβ). Its synthesis and coordination properties for CuΙ and CuΙΙ are described. L efficiently complex CuΙΙ in a square-planar geometry involving three imidazole nitrogen atoms and an amidate–Cu bond. By contrast, CuΙ is coordinated in a tetrahedral environment. The redox behavior is irreversible and follows an ECEC mechanism in accordance with the very different environments of the two redox states of the Cu center. This is in line with the observed resistance of the CuΙ complex to oxidation by oxygen and the CuΙΙ complex reduction by ascorbate. The affinities of L for CuΙΙ and CuΙ at physiological pH are larger than that reported for the Aβ peptide. Therefore, due to its peculiar Cu coordination properties, the ligand L is able to target both redox states of Cu, redox silence them and prevent reactive oxygen species production by the CuAβ complex. Because reactive oxygen species contribute to the oxidative stress, a key issue in Alzheimer's disease, this ligand thus represents a new strategy in the long route of finding molecular concepts for fighting Alzheimer's disease.
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Chemistry - A European Journal, Wiley-VCH Verlag, A Paraître, 〈10.1002/chem.201703429〉
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https://hal.archives-ouvertes.fr/hal-01635477
Contributeur : Christelle Hureau <>
Soumis le : mercredi 15 novembre 2017 - 11:25:16
Dernière modification le : mardi 5 décembre 2017 - 09:30:02

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Amandine Conte-Daban, Bastien Boff, Andreza Candido matias, Claudia N. Montes Aparicio, Christelle Gateau, et al.. A Trishistidine Pseudopeptide with Ability to Remove Both Cu Ι and Cu ΙΙ from the Amyloid-β Peptide and to Stop the Associated ROS Formation. Chemistry - A European Journal, Wiley-VCH Verlag, A Paraître, 〈10.1002/chem.201703429〉. 〈hal-01635477〉

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