A theoretical study of the electrostatic interactions in the intercalation model of the DNA-dye complex

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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“…3. In these experiments Mg+ 2 stabilizes the DNA helical structure and inhibits hydrocarbon intercalation (8,17,28). As expected, Panel A of Fig.…”

Section: Resultssupporting

confidence: 63%

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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“…A possible explanation is that the rigid polymer environment decreases possible non-radiative decay processes. Increasing the ionic strength will in general decrease the binding of intercalated dye molecules (Gilbert and Claverie, 1968;Record et al, 1976). In agreement with this it is observed that the decay rates of the MB+ triplet in complex with polynucleotides increase with the ionic strength of the solution as the binding equilibrium shifts towards non-intercalated or free dye.…”

Section: Discussionsupporting

confidence: 67%

LASER FLASH SPECTROSCOPY OF METHYLENE BLUE WITH NUCLEIC ACIDS. EFFECTS OF IONIC STRENGTH AND pH

Putten

Kelly

1989

Photochem & Photobiology

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Laser flash spectroscopic measurements were made on methylene blue complexed to the synthetic polynucleotides poly[d(G-C)] and poly[d(A-T)] in solutions of varying ionic strength and pH. Triplet decay rates and rates of triplet quenching by oxygen have been measured for the polymer/dye solutions. The triplet decay and oxygen quenching rates of methylene blue in complex with poly[d(A-T)] are much less sensitive than those with poly[d(G-C)] with respect to variations in ionic strength. It is also shown that protonation of the triplet state of MB+ with poly[d(A-T)] is slower than that of free dye. These results indicate strong binding of the dye to poly[d(A-T)]. Excitation of the MB+/poly[d(A-T)] complex at 665 nm yielded single exponential decay kinetics, in contrast with excitation at 600 nm where double exponential kinetics were measured. This is tentatively assigned to excitation of dye dimer bound to this polymer.

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“…Effect of Magnesium Ions. In the presence of magnesium ions (and of other cations), the repulsive effects between adjacent phosphate groups on the DNA backbone are reduced (Gilbert & Claverie, 1968), and the extent of binding of aromatic dye molecules (Chan & McCarter, 1970) is decreased. Accordingly (V. Ibanez and N. E. Geacintov, unpublished results) the extent of intercalative binding (as determined by the absorbance at 353 nm) of BPDE into DNA is reduced in the presence of Mg2+ ions.…”

Section: Resultsmentioning

confidence: 99%

Noncovalent binding of 7.beta.,8.alpha.-dihydroxy-9.alpha.,10.alpha.-epoxytetrahydrobenzo[a]pyrene to DNA and its catalytic effect on the hydrolysis of the diol epoxide to tetrol

Geacintov¹,

Yoshida²,

Ibáñez³

et al. 1982

Biochemistry

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In the presence of native DNA the hydrolysis of benzo[a]pyrene-7,8-diol 9,10-epoxide (BPDE) to tetrols (BPT) is markedly accelerated (by a factor of up to approximately 80 at 25 degrees C, pH 7.0, in 5 mM sodium cacodylate buffer solution). When stopped-flow kinetic techniques are utilized, it is shown that the pseudo-first-order hydrolysis rate constant kH is smaller by a factor of approximately 3 in the presence of equivalent concentrations of denatured DNA, by a factor of 8-25 in the presence of nucleotides, and by a factor of 35-45 in the presence of nucleosides (depending on the nucleotide or nucleoside). In the presence of native DNa, kH increases with increasing DNA concentration and reaches a limiting value of kH = 0.684 +/- 0.04 s-1 at DNA concentrations in excess of approximately 5 x 10(-4) M (expressed in concentration of nucleotides). A kinetic model based on (1) rapid formation of a noncovalent BPDE-DNA complex followed by (2) slower hydrolysis of BPDE to BPT at these binding sites is consistent with the experimental data. It is shown furthermore that the DNA concentration dependence of kH and of noncovalent intercalative binding of BPDE to DNA is similar and that addition of magnesium ions (which is known to reduce intercalative binding of planar aromatic molecules to DNA) also reduces kH. These results suggest, but do not necessarily prove, that the DNA binding sites at which the hydrolysis of BPDE (to BPT) is catalyzed are intercalative in nature.

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A theoretical study of the electrostatic interactions in the intercalation model of the DNA-dye complex

Cited by 23 publications

References 14 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

LASER FLASH SPECTROSCOPY OF METHYLENE BLUE WITH NUCLEIC ACIDS. EFFECTS OF IONIC STRENGTH AND pH

Noncovalent binding of 7.beta.,8.alpha.-dihydroxy-9.alpha.,10.alpha.-epoxytetrahydrobenzo[a]pyrene to DNA and its catalytic effect on the hydrolysis of the diol epoxide to tetrol

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