Guanine-Rich RNAs and DNAs That Bind Heme Robustly Catalyze Oxygen Transfer Reactions

Abstract

Diverse guanine-rich RNAs and DNAs that fold to form guanine quadruplexes are known to form tight complexes with Fe(III) heme. We show here that a wide variety of such complexes robustly catalyze two-electron oxidations, transferring oxygen from hydrogen peroxide to thioanisole, indole, and styrene substrates. Use of (18)O-labeled hydrogen peroxide reveals the source of the oxygen transferred to form thioanisole sulfoxide and styrene oxide to be the activated ferryl moiety within these systems. Hammett analysis of the kinetics of thioanisole sulfoxide formation is unable to distinguish between a one-step, direct oxygen transfer and a two-step, oxygen rebound mechanism for this catalysis. Oxygen transfer to indole produces a range of products, including indigo and related dyes. Docking of heme onto a high-resolution structure of the G-quadruplex fold of Bcl-2 promoter DNA, which both binds heme and transfers oxygen, suggests a relatively open active site for this class of ribozymes and deoxyribozymes. That heme-dependent catalysis of oxygen transfer is a property of many RNAs and DNAs has ramifications for primordial evolution, enzyme design, cellular oxidative disease, and anticancer therapeutics.

A Hemin/G‐Quadruplex Acts as an NADH Oxidase and NADH Peroxidase Mimicking DNAzyme

“…These systems pave the way to use the DNAzyme as a NAD + regeneration cycle for biocatalytic transformations and to implement the hemin/G-quadruplex as a catalyst for other chemical processes. Our systems complement the recently reported studies by Sen and co-workers [20] that demonstrated that hemin linked to G-rich RNAs and DNAs catalyze oxygen transfer reactions. All these novel biocatalytic functions of hemin/G-quadruplex suggest that further new processes might be catalyzed by this nanostructure.…”

Biomimetic Oxidation Reactions of a Naked Manganese(V)–Oxo Porphyrin Complex

“…[43] Although the performance of a correlation of the kinetic data with either s or s + values has been proposed to support either a one step, concerted oxygen transfer or a two step, electron-transfer mechanism, caution has been suggested against using this kind of evidence as definitive proof of reaction mechanism. [44] As shown in Table 2, the rate constants for gas-phase sulfoxidation decline from thioanisoles to dimethylsulfide, a trend similarly found in solution and considered to demonstrate a single ET process. [45] Recent theoretical calculations revealed that Cpd I models with thiolate or imidazole proximal ligands react with dimethylsulfide via a concerted, single-step OAT, with a ligand-dependent spin-state selectivity.…”

Characterization of the Interaction between Heme and a Parallel G-Quadruplex DNA Formed from d(TTAGGGT)

“…1317 Poon et al 18 also demonstrated that heme(Fe 3+ ) bound to the G-quartet of G-quadruplex DNAs and RNAs exhibits catalytic activity in oxygen transfer reactions. These findings have paved the way for exploring biological versatility of heme (Fe 3+ ) as prosthetic groups of DNAzymes and RNAzymes.…”