DNA nuclease activity of [Cu(dmp)2]+ and reactive specie involved in oxidative mechanism

Levín, Pedro; Gonzales, David; Escudero, Dayra; Romo, Adolfo I. B.; Lemus, luis

Keywords: DNA cleavage, Nucleases, reactive oxygen species


Metallic complexes capable to induce DNA cleavage, known as “artificial nucleases”, have been of great interest due to diverse applications in biotechnology and medicine for the treatment of diseases such as cancer, mainly because DNA is the primary target for cancer therapy.The nuclease activity of the bis-phenanthroline cuprous complex, [Cu(phen)2]+ (phen:1,10-phenanthroline), has been extensively studied and it has been concluded that the predominant mechanism of DNA cleavage corresponds to an oxidative attack of the C1‘ of the desoxyribose. Other related complexes with substituents at positions other than 2 and 9 on the phenanthroline ligand, have shown similar behaviour when are evaluated as nucleases. However, studies of the nuclease activity of the cuprous complex coordinated to 2,9dimethyl-1,10-phenanthroline (dmp), [Cu(dmp)2]+, have not shown the same behaviour yet. This lack of activity has been ascribed to the redox stability of the complex in the Cu(I) state, which limits its study as artificial nuclease. In this work, we present results of the nuclease activity of the [Cu(dmp)2]+ complex without the use of external agents as redox activators. The possible mechanism of oxidative damage is through the generation of reactive oxygen species (ROS), as observed by electrophoresis with the use of ROS scavengers. In the redox mechanism involved, the recuperation of the Cu(I) state from the oxidized Cu(II) complex, resulted to be mediated by water, which was studied by kinetic methods.

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Fecha de publicación: 2017
Año de Inicio/Término: 31 de julio al 4 de agosto
Idioma: Inglés