Cationic Anthraquinone Derivatives as Catalytic DNA Photonucleases: Mechanisms for DNA Damage and Quinone Recycling

Armitage, Bruce A.; Yu, Changjun; Devadoss, Chelladurai; Schuster, Gary B.

doi:10.1021/ja00101a005

Cited by 166 publications

(193 citation statements)

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“…Both have sufficient excited-state reduction potentials (2.0 and 1.9 V vs. NHE, respectively) (29,30) to oxidize each of the four natural DNA bases, and neither photoreduces DNA bases (31,32). Photoinduced electron transfer from r CP C to each of these oxidants is observed in solution.…”

Section: Resultsmentioning

confidence: 99%

Long-range oxidative damage to cytosines in duplex DNA

Shao

O’Neill²,

Barton³

2004

Proc. Natl. Acad. Sci. U.S.A.

140

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Charge transport (CT) through DNA has been found to occur over long molecular distances in a reaction that is sensitive to intervening structure. The process has been described mechanistically as involving diffusive charge-hopping among low-energy guanine sites. Using a kinetically fast electron hole trap, N4-cyclopropylcytosine ( CP C), here we show that hole migration must involve also the higher-energy pyrimidine bases. In DNA assemblies containing either [Rh(phi)2(bpy )] 3؉ or an anthraquinone derivative, two highenergy photooxidants, appreciable oxidative damage at a distant CP C is observed. The damage yield is modulated by lower-energy guanine sites on the same or complementary strand. Significantly, the efficiency in trapping at CP C is equivalent to that at N2-cyclopropylguanosine ( CP G). Indeed, even when CP G and CP C are incorporated as neighboring bases on the same strand, their efficiency of photodecomposition is comparable. Thus, CT is not simply a function of the relative energies of the isolated bases but instead may require orbital mixing among the bases. We propose that charge migration through DNA involves occupation of all of the DNA bases with radical delocalization within transient structure-dependent domains. These delocalized domains may form and break up transiently, facilitating and limiting CT. This dynamic delocalized model for DNA CT accounts for the sensitivity of the process to sequence-dependent DNA structure and provides a basis to reconcile and exploit DNA CT chemistry and physics.charge transport ͉ delocalized domain ͉ radical trap ͉ base dynamics O xidative damage to DNA from a distance through longrange migration of charge has now been established in many DNA assemblies by using different pendant photooxidants through both biochemical and spectroscopic assays (1-8). The DNA base pair stack can mediate charge transport (CT) over at least 200 Å (2, 3), and the reaction is exquisitely sensitive to the dynamic structure and stacking within the DNA duplex (9, 10). This sensitivity to perturbations in base pair stacking has been advantageous in the development of DNA-based sensors for mutational analysis (11) and may provide a role for DNAmediated CT within the cell (12), but it has limited the application of physical techniques to explore CT mechanistically.Although not a robust molecular wire, the DNA duplex has in some experiments been characterized as a wide band gap semiconductor (13,14). More prevalent have been models of incoherent CT involving a mixture of localized charge-hopping among low-energy sites, guanines and sometimes adenines, and tunneling through higher-energy pyrimidine bases (15-18). These mechanisms do not provide a rationale, however, for the sensitivity of CT to DNA structure. We have observed that DNA CT is gated by the dynamical motions of the DNA bases (9, 19) and have described DNA CT as conformationally gated hopping through transient, well stacked DNA domains (20).Our experimental strategy to probe for hole density on pyrimidines exploits the rapid ...

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Section: Resultsmentioning

confidence: 99%

Long-range oxidative damage to cytosines in duplex DNA

Shao

O’Neill²,

Barton³

2004

Proc. Natl. Acad. Sci. U.S.A.

140

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“…Breslin and Schuster (17) demonstrated unambiguously that GG-selective, photoinduced damage of DNA arises by an electron transfer pathway from an intercalated anthraquinone. Time-resolved spectroscopy reveals that the excited state of the quinone accepts an electron from a base in the DNA within 20 ps of excitation (21). The base radical cation (hole) can either recombine with the electron, be trapped by reaction with water and͞or oxygen, or migrate along the DNA helix to the lowest oxidation potential sites that serve as traps (22,23).…”

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confidence: 99%

Peptide nucleic acid–DNA duplexes: Long range hole migration from an internally linked anthraquinone

Armitage

Ly²,

Koch³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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The discovery that peptide nucleic acids (PNA) mimic DNA and RNA by forming complementary duplex structures following Watson-Crick base pairing rules opens fields in biochemistry, diagnostics, and medicine for exploration. Progress requires the development of modified PNA duplexes having unique and well defined properties. We find that anthraquinone groups bound to internal positions of a PNA oligomer intercalate in the PNA-DNA hybrid. Their irradiation with near-UV light leads to electron transfer and oxidative damage at remote GG doublets on the complementary DNA strand. This behavior mimics that observed in related DNA duplexes and provides the first evidence for long range electron (hole) transport in PNA-DNA hybrid. Analysis of the mechanism for electron transport supports hole hopping.Peptide nucleic acid (PNA) oligomers are DNA͞RNA analogs (see Fig. 1) in which the natural sugar-phosphate backbone is replaced by a synthetic peptide backbone (1). PNA oligomers that contain purine and pyrimidine nucleobases hybridize with complementary DNA and RNA strands to form right-handed, double-helical complexes according to the Watson-Crick rules of hydrogen bond-mediated base pair formation (2). Although much has been learned about the structural (3) and thermodynamic (4) factors involved in hybridization, little is known about the chemical reactivity of PNA͞DNA hybrids. It is crucial to understand how PNA͞DNA hybrids mimic the reactions and functions of duplex DNA. Of immediate importance for their application as clinical diagnostic agents is investigation of the conductivity of DNA and its PNA analogs (5, 6).DNA must balance the dual requirements of chemical stability and ease of transcription and replication (7). It is clear that DNA is far from inert toward a variety of different reactive species, particularly oxidizing agents. Oxidative damage to DNA produced by normal metabolism, deep-UV laser irradiation (8), gamma rays (9), or pulse radiolysis (10) accumulates at guanine residues, an effect attributed to one-dimensional migration of a radical cation (''hole'') along the DNA helix (11). Both the low oxidation potential and reactivity of the guanine radical cation contribute to the effectiveness of guanine as a trap for the migrating hole. Because guanine lesions may be the major cause of mutations (12), intense attention is focused on understanding the conductivity properties of DNA to elucidate the mechanisms by which migration of oxidative damage occurs (13). In this regard, the recent reports by Barton and coworkers are particularly important (14, 15). They describe a system consisting of a rhodium complex that is covalently linked to one end of a DNA duplex. Irradiation caused damage to the DNA more than 30 Å from where the complex was presumed to intercalate. This observation opens up exciting opportunities to study the factors that control hole migration in nucleic acids.Photosensitizers often react with nucleic acids by single electron transfer to oxidize a base. Recent findings reveal that the...

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“…It had been well documented that upon photoexcitation, the AQ moiety is able to undergo rapid intersystem crossing to generate long-lived triplet states that were capable of oxidizing the natural nucleobases. 15 The attachment of AQ to deoxyuridine via an acetylene linker would ensure strong electronic coupling with the DNA -stack and restrict the electronic injection at the anchoring site. AQ1 and AQ2 contain two guanine doublets, proximal and distal to the photooxidant, respectively.…”

Section: Resultsmentioning

confidence: 99%

Magnetic Fields Facilitate DNA-Mediated Charge Transport

et al. 2015

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Exaggerate radical-induced DNA damage under magnetic fields is of great concerns to medical biosafety and to biomolecular device based upon DNA electronic conductivity. In this report, the effect of applying an external magnetic field (MF) on DNA-mediated charge transport (CT) was investigated by studying guanine oxidation by a kinetics trap ( 8CP G) via photoirradiation of anthraquinone (AQ) in the presence of an external MF. Positive enhancement in CT efficiencies was observed in both the proximal and distal 8CP G after applying a static MF of 300 mT. MF assisted CT has shown sensitivities to magnetic field strength, duplex structures, and the integrity of base pair stacking. MF effects on spin evolution of charge injection upon AQ irradiation and alignment of base pairs to CT-active conformation during radical propagation were proposed to be the two major factors that MF attributed to facilitate DNA-mediated CT. Herein, our results suggested that the electronic conductivity of duplex DNA can be enhanced by applying an external MF. MF effects on DNA-mediated CT may offer a new avenue for designing DNA-based electronic device, and unraveled MF effects on redox and radical relevant biological processes.

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Cationic Anthraquinone Derivatives as Catalytic DNA Photonucleases: Mechanisms for DNA Damage and Quinone Recycling

Cited by 166 publications

References 0 publications

Long-range oxidative damage to cytosines in duplex DNA

Long-range oxidative damage to cytosines in duplex DNA

Peptide nucleic acid–DNA duplexes: Long range hole migration from an internally linked anthraquinone

Magnetic Fields Facilitate DNA-Mediated Charge Transport

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