Base-selective oxidation and cleavage of DNA by photochemical cosensitized electron transfer

Dunn, David A.; Lin, Vivian H.; Kochevar, Irene E.

doi:10.1021/bi00161a048

Cited by 71 publications

(61 citation statements)

References 27 publications

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“…11 (45). Having acetylenes in the meta arrangement eliminates both the Bergman and C1-C5 cyclization but the number of other possibilities remain, such as cross-link formation between dipeptides and DNA, alkylation of DNA nucleobases (46,47) and their oxidative damage initiated by electron transfer (48)(49)(50), hydrogen abstraction from the sugar moieties (51,52) and other reactions with reactive oxygen species (ROS) (53)(54)(55). Irradiation with UV light transforms the conjugates into the excited singlet states.…”

Section: Scavenger Experimentsmentioning

confidence: 99%

Opening Enediyne Scissors Wider: pH‐Dependent DNA Photocleavage by meta‐Diyne Lysine Conjugates

Kaya

Johnson

Alabugin

2015

Photochem & Photobiology

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Photochemical activation of meta-diynes incapable of Bergman and C1-C5 cyclizations still leads to efficient double-strand DNA cleavage. Spatial proximity of the two arylethynyl groups is not required for efficient DNA photocleavage by the enediyne-lysine conjugates. Efficiency of the cleavage is a function of the external pH and DNA damage is strongly enhanced at pH < 7. The pH-dependence of the DNA photocleavage activity stems from the protonation states of lysine amino groups, the internal electron donors responsible for intramolecular PET quenching and deactivation of the photoreactive excited states. DNA-binding analysis suggests intercalative DNA binding for phenyl substituted conjugate and groove binding for TFP-substituted conjugate. Additional insights in the possible mechanism for DNA damage from the ROS (Reactive Oxygen Species) scavenger experiments found that generation of singlet oxygen is partially involved in the DNA damage.

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Section: Scavenger Experimentsmentioning

confidence: 99%

Opening Enediyne Scissors Wider: pH‐Dependent DNA Photocleavage by meta‐Diyne Lysine Conjugates

Kaya

Johnson

Alabugin

2015

Photochem & Photobiology

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“…18 ET between guanosine nucleosides is favored because this nucleoside is the easiest to oxidize. 19,20 Netzel and colleagues also showed that the excited-state lifetimes of cyanine dyes are multiexponential and dependent on the composition of the dsDNA. 6 Similar findings have been reported by recent singlemolecule fluorescence studies using average decay-time distributions.…”

Section: Introductionmentioning

confidence: 99%

Binding of BOBO-3 Intercalative Dye to DNA Homo-Oligonucleotides with Different Base Compositions

et al. 2010

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The interactions between trimethine cyanine homodimer dye, BOBO-3 (1,1'-(4,4,7,7-tetramethyl-4,7-diazaundecamethylene)-bis-4-[3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene]-pyridinium tetraiodide), and single-stranded homo-oligonucleotides, double-stranded complementary homo-oligonucleotides, and high-molecular-weight double-stranded polyhomonucleotides have been investigated in detail using absorption and both steady-state and time-resolved fluorescence spectroscopy. In this work, we describe the differences in the binding behavior of BOBO-3 with double-stranded DNA (dsDNA) having different base contents. The fluorescence intensity of BOBO-3 interacting with deoxyadenosine-deoxythymidine (dAdT) dsDNA was higher than with the deoxyguanosine-deoxycytidine (dGdC) double helix. However, the BOBO-3 lifetime was longer in dGdC-rich dsDNA than in dsDNA with many dAdT sites. This result was detected at both the ensemble level and the single-molecule level. This behavior is a consequence of the dye's interacting with dsDNA on two kinds of binding sites. This phenomenon also occurs in natural dsDNA (Ruedas-Rama, M. J.; Orte, A.; Crovetto, L.; Talavera, E. M.; Alvarez-Pez, J. M. J. Phys. Chem. B 2010, 114, 1094-1103). By using a time-resolved fluorescence methodology and the McGhee-von Hippel theory for two overlapping, noncooperative binding modes, we obtained the equilibrium binding constants and the number of occupied sites for each binding mode of BOBO-3 in dAdT and dGdC binding sites. BOBO-3 has a higher affinity for dAdT sites and occupies 4.0 +/- 1.0 sites in its primary binding mode, whereas in dGdC-rich double strands, BOBO-3 covers 6.2 +/- 1.1 sites and has a lower affinity. These differences in the binding features and spectral properties of BOBO-3 may be used to develop approaches to identify GC- or AT-rich regions within large strands of dsDNA.

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“…[20] However, compounds that exhibit considerable DNA binding affinity and specificity in cleavage are yet to be achieved.…”

Section: Introductionmentioning

confidence: 99%

Design of Photoactivated DNA Oxidizing Agents: Synthesis and Study of Photophysical Properties and DNA Interactions of Novel Viologen‐Linked Acridines

Joseph

Eldho

Ramaiah

2003

Chemistry A European J

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A new series of photoactivated DNA oxidizing agents in which an acridine moiety is covalently linked to viologen by an alkylidene spacer was synthesized, and their photophysical properties and interactions with DNA, including DNA cleaving properties, were investigated. The fluorescence quantum yields of the viologen-linked acridines were found to be lower than that of the model compound 9-methylacridine (MA). The changes in free energy for the electron transfer reactions were found to be favorable, and the fluorescence quenching observed in these systems is explained by an electron transfer mechanism. Intramolecular electron transfer rate constants were calculated from the observed fluorescence quantum yields and singlet lifetime of MA and are in the range from 1.06x10(10) s(-1) for 1 a (n=1) to 6x10(8) s(-1) for 1 c (n=11), that is, the rate decreases with increasing spacer length. Nanosecond laser flash photolysis of these systems in aqueous solutions showed no transient absorption, but in the presence of guanosine or calf thymus DNA, transient absorption due to the reduced viologen radical cation was observed. Studies on DNA binding demonstrated that the viologen-linked acridines bind effectively to DNA in both intercalative and electrostatic modes. Results of PM2 DNA cleavage studies indicate that, on photoexcitation, these molecules induce DNA damage that is sensitive to formamidopyrimidine DNA glycosylase. These viologen-linked acridines are quite stable in aqueous solutions and oxidize DNA efficiently and hence can be useful as photoactivated DNA-cleaving agents which function purely by the co-sensitization mechanism.

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Base-selective oxidation and cleavage of DNA by photochemical cosensitized electron transfer

Cited by 71 publications

References 27 publications

Opening Enediyne Scissors Wider: pH‐Dependent DNA Photocleavage by meta‐Diyne Lysine Conjugates

Opening Enediyne Scissors Wider: pH‐Dependent DNA Photocleavage by meta‐Diyne Lysine Conjugates

Binding of BOBO-3 Intercalative Dye to DNA Homo-Oligonucleotides with Different Base Compositions

Design of Photoactivated DNA Oxidizing Agents: Synthesis and Study of Photophysical Properties and DNA Interactions of Novel Viologen‐Linked Acridines

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