Effects of Heme Electronic Structure and Local Heme Environment on Catalytic Activity of a Peroxidase-Mimicking Heme-DNAzyme

The catalytic cycle of a peroxidase-mimicking heme-DNAzyme involves an iron(IV)oxo porphyrin pi-cation radical intermediate known as compound I formed through heterolytic O-O bond cleavage of an Fe3+-bound hydroperoxo ligand (Fe-OOH) in compound 0, like that of a heme enzyme such as horseradish peroxidase (HRP). Peroxidase assaying of complexes composed of chemically modified hemes possessing various electron densities of the heme iron atom (rho(Fe)) and parallel-stranded tetrameric G-quadruplex DNAs of oligonucleotides d(TTAGGG), d(TTAGGGT), and d(TTAGGGA) was performed to elucidate the effects of the heme electronic structure and local heme environment on the catalytic activity of the heme-DNAzyme. The study revealed that the DNAzyme activity is enhanced through an increase in the rho(Fe) and general base catalysis of the adenine base adjacent to the heme, which are reminiscent of the push and pull mechanisms in the catalytic cycle of HRP, respectively, and that the activity of the heme-DNAzyme can be independently controlled through the heme electronic structure and local heme environment. These findings allow a deeper understanding of the structure-function relationship of the peroxidase-mimicking heme-DNAzyme.

Automated summary

The catalytic cycle of a peroxidase-mimicking heme-DNAzyme involves an intermediate known as compound I, formed through O-O bond cleavage of an Fe3+-bound hydroperoxo ligand. Peroxidase assaying was performed to elucidate the effects of heme electronic structure and local heme environment on catalytic activity. The study revealed that the activity of the heme-DNAzyme can be controlled independently through heme electronic structure and local environment, enhancing the understanding of the structure-function relationship.