Effect of DNA molecular weight, temperature, and magnetic field strength on the phosphorus-31 NMR results of DNA complexed with ethidium

Wilson, W. David; Keel, Rebecca A.; Mariam, Yitbarek H.

doi:10.1021/ja00410a070

Cited by 28 publications

(16 citation statements)

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“…A second peak was not generated upon addition of PhIP (upper spectrum), suggesting that PhIP is in fast exchange with the DNA. The chemical shift of DNA phosphates is a sensitive function of the DNA backbone torsional angles (42,43), and the data suggests a non-intercalative mode of DNA binding by PhIP since ligand-base stacking interactions consistently induce downfield shifts in the phosphorus resonances (42)(43)(44)(45).…”

Section: Resultsmentioning

confidence: 96%

Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Marsch¹,

Ward²,

Colvin³

et al. 1994

Nucl Acids Res

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The cooked meat mutagen 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) is metabolized in vivo to electrophilic intermediates that covalently bind to DNA guanines. Here we address the mechanism of PhIP's non-covalent interaction with DNA by using spectroscopic and computational methodologies. NMR methodologies indicated that upon addition of DNA, PhIP aromatic protons underwent a small, 0.11-0.12 p.p.m. upfield shift. DNA phosphorus resonances of non-covalent PhIP-DNA complexes broadened and slightly shifted upfield, while DNA base imino proton resonances shifted slightly downfield relative to DNA alone. UV and fluorescence spectra of PhIP titrated with DNA showed no detectable shifting and hypochromism of absorbance or fluorescence bands. In the presence of DNA, PhIP fluorescence was efficiently quenched by acrylamide, but not by silver ion. Further, the NMR spectra suggest that PhIP is in fast exchange with the DNA, and is slightly specific for adenine-thymine (A-T) sequences. Finally, structural arguments based on quantum chemistry calculations suggested that PhIP and its metabolites are unlikely to intercalate into DNA. These data collectively indicate that PhIP non-covalently binds in a groove of DNA.

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Section: Resultsmentioning

confidence: 96%

Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Marsch¹,

Ward²,

Colvin³

et al. 1994

Nucl Acids Res

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“…Because of the potential sensitivity of 31P chemical shifts to phosphate bond and tortional angles, this method is a valuable addition to techniques for monitoring conformational changes in DNA (9). We have shown that the DNA chemical shift is sensitive to temperature (4), interaction with simple metal species (10), platinum antitumor agents (10), and intercalating drugs (11,12). Temperature (4) intercalating drugs (11,12), platinum antitumor agents (10), and HgC12 (10) cause downfield shifts in the DNA 31P signal while magnesium and calcium ions cause upfield shifts (10).…”

Section: Introductionmentioning

confidence: 99%

Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:³¹P NMR chemical shift and relaxation investigation

Wilson

Jones

1982

Nucl Acids Res

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The binding of actinomycin D, ethidium, quinacrine, daunorubicin, and tetralysine to DNA has been investigated using 31P NMR. Titration of DNA with actinomycin yields a new downfield peak or overlapping peaks as would be expected from the slow dissociation kinetics of this compound. The other intercalators shift the DNA 31P signal downfield as a single exchange averaged peak. Tetralysine causes a slight upfield shift. The chemical shift titration curves for the intercalators are sigmoid curves suggesting that cooperative processes or competing effects on the chemical shift are being observed. The magnitude of the chemical shift change at saturation of DNA with the compounds is found to vary significantly and to be linearly related to the DNA base pair unwinding angle for the compounds. Analysis of 31P spin lattice relaxation times (T1) and linewidths as a function of temperature (below Tm) and titration with the above compounds indicates that T1 does not change significantly while linewidth increases with decreasing temperature and increasing bound intercalator. One interpretation of these results is that in both cases the overall motion of DNA becomes slower while the internal motion is not greatly affected.

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“…The deoxyribose-phosphate backbone surrounding each ethidium site is also subject to sizable internal motions, although the IH-and 31P-relaxation times associated with dye binding may be indicative of slightly more restricted variations of the chain than in the free polynucleotide helix. 95 The flexibility of a nucleic acid-drugldye complex is also governed by the chemical nature of the intercalating species, which for reasons of simplicity were ignored in this study. Specific interactions of ligand with the sugar-phosphate backbone or surrounding bases are likely to favor the occurrence of certain nucleic acid conformers over others.…”

Section: Discussionmentioning

confidence: 99%

Theoretical studies of nucleic acid interactions. I. Estimates of conformational mobility in intercalated chains

Taylor

Olson

1983

Biopolymers

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SynopsisA combined geometric and potential-energy analysis has been carried out to identify the torsional arrangements of the nucleic acid chain that can accommodate the intercalation of small planar moieties. In contrast to previous theoretical efforts, which detail local conformations after adjacent bases are positioned in space, the likely geometries are found here on the basis of the base orientations that result from all feasible combinations of the nine torsional variables of the basic dinucleotide intercalation unit. The relatively mobile nature of the sugar-phosphate backbone, together with the fairly long stretches of chemical bonds between adjacent units, is apparently responsible for the large number of feasible binding geometries. Some previously overlooked conformations with unusual sugar-puckering combinations and various phosphodiester arrangements are found in the survey. A large proportion of the energetically favored intercalation states are closely related to the backbone conformations of familiar double-helical models such as A-, B-, and Z-DNA, as well as the Watson-Crick model. Moreover, the intercalated forms are found to interconvert smoothly along a continuous conformational pathway. The intercalation structures derived from x-ray crystallographic analyses of drug-oligonucleotide complexes, in contrast, are stiff three-dimensional forms essentially frozen in a single domain of conformation space. Specific ligand-nucleic acid interactions that may he responsible for the experimental observations are not included in this study. The classical intramolecular potential energies reported here are highly approximate, providing only rough gauges of the relative importance of the many competing conformations.

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Effect of DNA molecular weight, temperature, and magnetic field strength on the phosphorus-31 NMR results of DNA complexed with ethidium

Cited by 28 publications

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Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:³¹P NMR chemical shift and relaxation investigation

Theoretical studies of nucleic acid interactions. I. Estimates of conformational mobility in intercalated chains

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Effect of DNA molecular weight, temperature, and magnetic field strength on the phosphorus-31 NMR results of DNA complexed with ethidium

Cited by 28 publications

References 0 publications

Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:31P NMR chemical shift and relaxation investigation

Theoretical studies of nucleic acid interactions. I. Estimates of conformational mobility in intercalated chains

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Interaction of actinomycin D, ethidium quinacrine daunorubicin, and tetralysine with DNA:³¹P NMR chemical shift and relaxation investigation