DNA-Based Peroxidation Catalyst-What Is the Exact Role of Topology on Catalysis and Is There a Special Binding Site for Catalysis?

• Published in: Chemistry : a European journal 2011-05, Vol.17 (20), p.5691-5698
• Main Authors: Nakayama, Shizuka, Wang, Jingxin, Sintim, Herman O.
• Format: Article
• Language: English
• Subjects: Binding Sites; Biosensors; Catalysis; Catalysts; Chemical reactions; Chemistry; Cofactors; Covalence; Data processing; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA structures; DNA, Catalytic - metabolism; Enzymes; G-Quadruplexes; Hemin; Hemin - chemistry; Hemin - metabolism; Molecular Structure; nucleic acids; Peroxidase; Peroxidases - metabolism; Peroxidation; Ribonucleic acids; RNA; Structure-Activity Relationship; Topology
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201002349

In the last decade, there has been growing interests in studies aimed at delineating the strategies used by various nucleic acid enzymes to facilitate catalysis. Insights gained from such studies would enable the design of better DNA/RNA catalysts for various applications such as biosensing. DNA and RNA catalysts have been shown to be able to catalyze myriads of reactions, including peroxidation reactions, which are catalyzed by G‐quadruplexes. In this report, we provide data that clarifies how G‐quadruplex peroxidases achieve catalysis. Firstly, we show that by covalently linking a hemin cofactor to DNAzymes, anti‐parallel G‐quadruplexes, which have been previously shown to be catalytically inefficient, can be “resurrected” to become good peroxidation catalysts. We also reveal that the relative rates of peroxidation by DNAzyme peroxidases depend on the nature of the organic reductant, arguing for a special binding site in the peroxidase‐mimicking DNAzymes for catalysis. Topsy‐turvy activity: Anti‐parallel G‐quadruplexes are known to be poor peroxidation catalysts. This paper demonstrates that the covalent attachment of a hemin cofactor to G‐quadruplexes that form anti‐parallel topology promotes the formation of parallel/mixed‐hybrid structures and turns a bad peroxidation catalyst into an excellent catalyst (see figure).