4′‐Pivaloyl Substituted Thymidine as a Precursor for the Thymyl Radical: An EPR Spectroscopic Study

Schiemann, Olav; Feresin, Emiliano; Carl, Thomas; Giese, Bernd

doi:10.1002/cphc.200300896

Cited by 11 publications

(9 citation statements)

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“…One option was that the nucleic acid base could interact with the sugar radical resulting in the delocalization of the radical onto the base. (46) This proposal seemed unlikely as Perrson had reported (no data was shown) that interaction of E441Q-α 2 with GDP/TTP gave rise to a similar radical and a purine base is distinctly different from the pyrimidine base. However, at this stage, the identity of II was a real mystery, thus the importance of the base was further investigated using [5, 6- 2 H], [U− 15 N], [U− 13 C, 15 N] CDP with E441Q-α 2 .…”

Section: Resultsmentioning

confidence: 98%

Structure of the Nucleotide Radical Formed during Reaction of CDP/TTP with the E441Q-α2β2 ofE. coliRibonucleotide Reductase

et al. 2008

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The Escherichia coli ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleotides and requires a diferric-tyrosyl radical cofactor for catalysis. RNR is composed of a 1:1 complex of two homodimeric subunits: α and β. Incubation of the E441Q-α mutant RNR with substrate CDP and allosteric effector TTP results in loss of the tyrosyl radical and formation of two new radicals on the 200 ms to min time scale. The first radical was previously established by stopped flow UV/vis spectroscopy and pulsed high field EPR spectroscopy to be a disulfide radical anion. The second radical was proposed to be a 4′-radical of a 3′-keto-2′-deoxycytidine 5′-diphosphate. To identify the structure of the nucleotide radical [1′-2H], [2′-2H], [4′-2H], [5′-2H], [U−13C, 15N], [U−15N], and [5,6 -2H] CDP and [β-2H] cysteine-α were synthesized and incubated with E441Q-α2β2 and TTP. The nucleotide radical was examined by 9 GHz and 140 GHz pulsed EPR spectroscopy and 35 GHz ENDOR spectroscopy. Substitution of 2H at C4′ and C1′ altered the observed hyperfine interactions of the nucleotide radical and established that the observed structure was not that predicted. DFT calculations (B3LYP/IGLO-III/B3LYP/TZVP) were carried out in an effort to recapitulate the spectroscopic observations and lead to a new structure consistent with all of the experimental data. The results indicate, unexpectedly, that the radical is a semidione nucleotide radical of cytidine 5′-diphosphate. The relationship of this radical to the disulfide radical anion is discussed.

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Section: Resultsmentioning

confidence: 98%

Structure of the Nucleotide Radical Formed during Reaction of CDP/TTP with the E441Q-α2β2 ofE. coliRibonucleotide Reductase

et al. 2008

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“…The measured ESR signals are similar to those that have been obtained for the unsubstituted thymine radical in frozen solution. 270 The lessnegative redox potential of thymine 132,249,250 compared to those of dialkyl ketones 320 provides the thermodynamic basis to reduce an adjacent thymine base.…”

Section: Fig 22 Comparison Between the T-t Dimer And Br-du As Kinetic...mentioning

confidence: 99%

Electron transfer processes in DNA: mechanisms, biological relevance and applications in DNA analytics

Wagenknecht

2006

Nat. Prod. Rep.

124

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In principle, DNA-mediated charge transfer processes can be categorized as oxidative hole transfer and reductive electron transfer. With respect to the routes of DNA damage most of the past research has been focused on the investigation of oxidative hole transfer or transport. On the other hand, the transport or transfer of excess electrons has a large potential for biomedical applications, mainly for DNA chip technology.

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“…That hydrogen atom transfer reactions between carbohydrate radicals and nucleotide bases can occur quite rapidly has recently been reported by Giese et al . in spectroscopic studies of C4' thymidine radicals, where the rearranged C5 thymyl radical could be detected as one of the main open-shell species by EPR spectroscopy [34]. (b) An alternative set of pathways exists in which the unpaired spin never leaves the ribose unit.…”

Section: Resultsmentioning

confidence: 99%

Transfer Hydrogenation in Open-Shell Nucleotides — A Theoretical Survey

Achrainer

Zipse

2014

Molecules

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Abstract:The potential of a larger number of sugar models to act as dihydrogen donors in transfer hydrogenation reactions has been quantified through the calculation of hydrogenation energies of the respective oxidized products. Comparison of the calculated energies to hydrogenation energies of nucleobases shows that many sugar fragment radicals can reduce pyrimidine bases such as uracil in a strongly exothermic fashion. The most potent reducing agent is the C3' ribosyl radical. The energetics of intramolecular transfer hydrogenation processes has also been calculated for a number of uridinyl radicals. The largest driving force for such a process is found for the uridin-C3'-yl radical, whose rearrangement to the C2'-oxidized derivative carrying a dihydrouracil is predicted to be exothermic by 61.1 kJ/mol in the gas phase.

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4′‐Pivaloyl Substituted Thymidine as a Precursor for the Thymyl Radical: An EPR Spectroscopic Study

Cited by 11 publications

References 51 publications

Structure of the Nucleotide Radical Formed during Reaction of CDP/TTP with the E441Q-α2β2 ofE. coliRibonucleotide Reductase

Structure of the Nucleotide Radical Formed during Reaction of CDP/TTP with the E441Q-α2β2 ofE. coliRibonucleotide Reductase

Electron transfer processes in DNA: mechanisms, biological relevance and applications in DNA analytics

Transfer Hydrogenation in Open-Shell Nucleotides — A Theoretical Survey

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