Fluorescence and photoelectron studies of the intercalative binding of benz(a)anthracene metabolite models to DNA

Shahbaz, M.; Harvey, Ronald G.; Prakash, A. S.; Boal, T.R.; Zegar, Irene S.; Lebreton, Pierre

doi:10.1016/0006-291x(83)91788-6

Cited by 12 publications

(7 citation statements)

References 10 publications

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“…Studies from this laboratory have shown that different metabolites formed from benz(a)anthracene exhibit different physical binding properties with DNA (19,20). The results from the present studies further characterize the physical binding properties of DMBA metabolites with DNA.…”

supporting

confidence: 63%

“…Previous studies indicate that 5,6-dihydro-BA has an intercalation association constant approximately equal to that of model2 (19).…”

Section: Discussionmentioning

confidence: 94%

“…In earlier fluorescence quenching studies of 1,2,3,4-tetrahydro-BA, which, like DMA, is a rr electron modd of the bay region epoxide of DMBA, it was found that DNA intercalation readily occurs (19,20). On the other hand, molecule 2 was found to have very different DNA binding characteristics.…”

mentioning

confidence: 95%

“…For these hydrocarbons the fluorescence intensity {1 0 ) measured without DNA is greater than the intensity (I) measured with DNA. In cases (21) where dynamic quenching of the hydrocarbon by DNA is small, and where the bound hydrocarbon has negligible fluorescence quantum yield compared to that of the unquenched hydrocarbon the association constant, K 0 , for binding to the quenching site on DNA is given by In previous studies (19) with model compound 2 we found that at the DNA concentrations studied here dynamic quenching by DNA of hydrocarbons with fluorescence lifetimes below 35 nsec is insignificant. In the present studies the simplifying constraint which is inherent in Eq.…”

mentioning

confidence: 96%

“…On the other hand, molecule 2 was found to have very different DNA binding characteristics. Earlier attempts (19,20) to characterize the DNA and mononucleotide binding of 8,9,10,11-tetrahydro-BA were made difficult because the fluorescence intensity of this molecule under the experimental conditions employed was much lower than the intensities of the bay region models.…”

mentioning

confidence: 99%

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Intercalative DNA Binding of Model Compounds Derived From Metabolites of 7, 12-Dimethylbenz[a]anthracene

Zegar

Prakash

Lebreton

1984

Journal of Biomolecular Structure and Dynamics

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The DNA binding of nonreactive model compounds of metabolites of 7,12-dimethylbenz[a]-anthracene (DMBA)1 was studied in fluorescence quenching and fluorescence lifetime experiments. The model compounds examined were DMA and 8,9,10,11-tetrahydro-BA. DMA is a pi electron model of a highly carcinogenic bay region epoxide of DMBA, 8,9,10,11-tetrahydro-BA is a model compound of a less carcinogenic DMBA epoxide. The results indicate that the binding of DMA occurs primarily via intercalation. In 15% methanol the binding constant is 3.1 x 10(3) M-1. In 15% methanol and at DNA phosphate levels of 5.0 x 10(-4) M the intercalative binding of DMA is reduced by a factor of 6.2 when 5.0 x 10(-4) M Mg+2 is added. The DMA binding constant for intercalation is reduced by more than a factor of 4 when the methanol content of the solvent is increased from 0% to 20%. Finally DMA binding arising from pi interactions with the DNA bases is reduced more than 15 times when the DNA is denatured. For 8,9,10,11-tetrahydro-BA in 15% methanol the binding constant for intercalation is 6 times lower than that for DMA. These results along with previously reported binding data on other model compounds suggest that bay region metabolites of DMBA readily participate in physical pi stacking interactions with DNA.

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supporting

confidence: 63%

“…Previous studies indicate that 5,6-dihydro-BA has an intercalation association constant approximately equal to that of model2 (19).…”

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 95%

mentioning

confidence: 96%

mentioning

confidence: 99%

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Intercalative DNA Binding of Model Compounds Derived From Metabolites of 7, 12-Dimethylbenz[a]anthracene

Zegar

Prakash

Lebreton

1984

Journal of Biomolecular Structure and Dynamics

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SCC‐DFTB‐D study of intercalating carcinogens: Benzo(a)pyrene and its metabolites complexed with the G–C base pair

Kumar

Elstner

Suhai

2003

Int J of Quantum Chemistry

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ABSTRACT:The interaction of benzo(a)pyrene (BP) and its metabolites with the G-C base pair has been studied using the self-consistent-charge, density functional tightbinding(SCC-DFTB-D) method, augmented by the empirical London dispersion energy term. Structures of the complexes corresponding to a minimum interaction energy obtained using a constrained rigid body search were fully optimized. It is found that the benzylic ring of BP and its anti-conformers is located below the NH 2 group of guanine while the syn-conformers exhibit a different binding pattern. The BP triol carbocation (BPTC) in the anti-conformation is stabilized by an additional hydrogen bond between the hydrogen atom of the OH group of BPTC and the N 3 atom of guanine of the G-C base pair. The benzylic ring of BPTC directed toward the minor groove side whereas the pyrenyl ring stacks below the cytosine covering the hydrogen bond region. Guanine bends toward the benzylic ring, making an angle of ϳ11-15°w ith the pyrene ring. The calculated equilibrium structures are in good agreement with the available experimental and other theoretical results.

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Stereoelectronic aspects of the intercalative binding of benz[a]anthracene metabolite models to DNA

Prakash

Zegar

Shahbaz

et al. 2009

Int. J. Quantum Chem.

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The physical binding of m-electron models of different benz [a]anthracene metabolites to DNA exhibits widely varying properties. In this study, the binding properties of two nonreactive m-electron models of reactive metabolites of benz[a]anthracene were examined. The models investigated are 1,2,3,4-tetrahydrobenz[a]anthracene and 8,9,10,Il-tetrahydrobenz[n]anthracene. Physical binding has been studied by measuring the effects of native DNA, denatured DNA, and DNA components upon the fluorescence intensities and the fluorescence lifetimes of these models. The results indicate that both metabolite models bind to native DNA with association constants that are approximately equal and lie in the range of 2.0 to 3.0 x 103M-'. Furthermore, for both models, binding involves 1-electron interactions between the hydrocarbons and the nucleotide bases. However, the two models exhibit DNA complex conformations that are very different. Results indicate that 1,2,3,4-tetrahydrobenz[a]anthracene binding depends strongly upon DNA secondary structure and involves intercalated complexes. On the other hand, 8,9,10,11-tetrahydrobenz[a]anthracene binding is only weakly dependent upon DNA secondary structure. In native DNA, this binding involves wedged complexes. These two types of complexes may be representative of two important classes of conformations which occur when reactive hydrocarbon metabolites bind to DNA.

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Fluorescence and photoelectron studies of the intercalative binding of benz(a)anthracene metabolite models to DNA

Cited by 12 publications

References 10 publications

Intercalative DNA Binding of Model Compounds Derived From Metabolites of 7, 12-Dimethylbenz[a]anthracene

Intercalative DNA Binding of Model Compounds Derived From Metabolites of 7, 12-Dimethylbenz[a]anthracene

SCC‐DFTB‐D study of intercalating carcinogens: Benzo(a)pyrene and its metabolites complexed with the G–C base pair

Stereoelectronic aspects of the intercalative binding of benz[a]anthracene metabolite models to DNA

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