Metalloenzyme-mimic innate G-quadruplex DNAzymes using directly coordinated metal ions as active centers

Abstract

G-quadruplex DNAs (G4s) have been reported to exhibit the DNAzyme activities by binding with some metal complexes and functional organic ligands. However, there is a challenge to develop metalloenzyme-mimic G4-based innate DNAzymes using the complexed metal ions directly serving as the active centers. This will diversify DNAzymes for developing novel devices since G4 structures are more polymorphic than the other DNA foldings. In this work, we found that the lanthanide trivalent cerium ion of Ce³⁺ can bind to the human telomere G4 (htG4) according to a 1 : 2 binding mode favorable for creating metalloenzymes-mimic G4 DNAzymes. This Ce³⁺-G4 entity exhibits a peroxidase activity towards the oxidation of the substrate of 3,3,5,5-tetramethylbenzidine (TMB) by hydrogen peroxide. The 5′ G4 tetrads with the orderly arranged carbonyl oxygen atoms are believed to be the coordination sites for Ce³⁺ and favor the conversion between Ce³⁺ and Ce⁴⁺. Our work provides an alternative feasibility in developing the G4-based innate DNAzymes for variant applications.