A Trishistidine Pseudopeptide with Ability to Remove Both Cu-I and Cu-II from the Amyloid-beta Peptide and to Stop the Associated ROS Formation

Autor(es):Mostrar menos -

Conte-Daban, Amandine ^{[1, 2]} ; Boff, Bastien ^[3] ; Matias, Andreza Candido ^{[3, 4]} ; Aparicio, Claudia N. Montes ^{[1, 2]} ; Gateau, Christelle ^[3] ; Lebrun, Colette ^[3] ; Cerchiaro, Giselle ^[4] ; Kieffer, Isabelle ^{[5, 6]} ; Sayen, Stephanie ^[7] ; Guillon, Emmanuel ^[7] ; Delangle, Pascale ^[3] ; Hureau, Christelle ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] CNRS, LCC, 205 Route Narbonne, BP 44099, F-31077 Toulouse 4 - France

^[2] Univ Toulouse, UPS, INPT, F-31077 Toulouse 4 - France

^[3] Univ Grenoble Alpes, CNRS, CEA, INAC, SyMMES, UMR 5819, CIBEST, 17 Rue Martyrs, F-38000 Grenoble - France

^[4] Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210580 Santo Andre, SP - Brazil

^[5] ESRF, FAME Beamline BM30B, F-38043 Grenoble 9 - France

^[6] Univ Grenoble Alpes, CNRS, UMS 832, Observ Sci Univers Grenoble, F-38041 Grenoble - France

^[7] Univ Reims, CNRS, UMR 7312, ICMR, F-51687 Reims 2 - France

• Tipo de documento: Artigo Científico
• Fonte: CHEMISTRY-A EUROPEAN JOURNAL; v. 23, n. 67, p. 17078-17088, DEC 1 2017.
• Citações Web of Science: 10

Resumo

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 (A). Its synthesis and coordination properties for Cu and Cu are described. L efficiently complex Cu in a square-planar geometry involving three imidazole nitrogen atoms and an amidate-Cu bond. By contrast, Cu 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 Cu complex to oxidation by oxygen and the Cu complex reduction by ascorbate. The affinities of L for Cu and Cu at physiological pH are larger than that reported for the A 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 CuA 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. (AU)

• Processo FAPESP: 12/06754-4 - Síntese, caracterização e aplicação de ligantes do tipo tripodal com seletividade para Cu(II) no meio celular
• Beneficiário: Andreza Cândido Matias
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto