A hemeDNAzyme activated by hydrogen peroxide catalytically oxidizes thioethers by direct oxygen atom transfer rather than by a Compound I-like intermediate. Issue 4 (21st January 2021)

• Record Type: Journal Article
• Authors: Shumayrikh, Nisreen M; Warren, Jeffrey J; Bennet, Andrew J; Sen, Dipankar
• Is Part Of: Nucleic acids research. Volume 49:Issue 4(2021)
• Page Start: 1803
• Page End: 1815
• Publication Date: 2021-01-21
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkab007
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Hemin [Fe(III)-protoporphyrin IX] is known to bind tightly to single-stranded DNA and RNA molecules that fold into G-quadruplexes (GQ). Such complexes are strongly activated for oxidative catalysis. These hemeDNAzymes and ribozymes have found broad utility in bioanalytical and medicinal chemistry and have also been shown to occur within living cells. However, how a GQ is able to activate hemin is poorly understood. Herein, we report fast kinetic measurements (using stopped-flow UV–vis spectrophotometry) to identify the H2 O2 -generated activated heme species within a hemeDNAzyme that is active for the oxidation of a thioether substrate, dibenzothiophene (DBT). Singular value decomposition and global fitting analysis was used to analyze the kinetic data, with the results being consistent with the hemeDNAzyme's DBT oxidation being catalyzed by the initial Fe(III)heme–H2 O2 complex. Such a complex has been predicted computationally to be a powerful oxidant for thioether substrates. In the hemeDNAzyme, the DNA GQ enhances both the kinetics of formation of the active intermediate as well as the oxidation step of DBT by the active intermediate. We show, using both stopped flow spectrophotometry and EPR measurements, that a classic Compound I is not observable during the catalytic cycle for thioether sulfoxidation.