Sequence Selectivity, a Test of the Nature of the Covalent Adduct Formed Between Benzo[a]pyrene and DNA

Zakrzewska, K.; Pullman, Bernard

doi:10.1080/07391102.1987.10507682

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…In general, the yield patterns were different (17) from those reported here using single-stranded oligonucleotides. There is evidence that, in the case of native duplex DNA, the effects of base sequence extend beyond those flanking the modified G since enhanced binding of (±)-antt-BPDE was found at some, though not all, guanine-rich sequences (36)(37)(38)(39), possibly because of sequence-dependent local microconformation effects (36,40).…”

Section: Discussionmentioning

confidence: 99%

Base-sequence dependence of covalent binding of benzo[a]pyrenediol epoxide to guanine in oligodeoxyribonucleotides

Margulis

Ibáñez

Geacintov³

1993

Chem. Res. Toxicol.

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The base-sequence dependence of the yield of the covalent binding reaction of (+)-anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] with the exocyclic amino group of guanine surrounded by different flanking bases X and Y in the single-stranded oligonucleotide d(CTATXGYTATC) was investigated. With an initial ratio of [(+)-anti-BPDE]/[oligonucleotide strand] = 2, the percentage of modified strands varied from 20 +/- 2% when the modified dG was surrounded by pyrimidines to 5-7% when the central dG was surrounded by purines. The trans/cis ratio of (+)-anti-BPDE-N2-dG adducts was in the range of 3-5. The lower reaction yields observed when the modified guanine residues in single-stranded oligonucleotides are surrounded by purines rather than by pyrimidines is tentatively attributed (1) to steric effects arising from the presence of the bulkier purines flanking the reacting dG moieties on the 5'- and 3'-sides and/or (2) to noncovalent interactions between anti-BPDE and neighboring purines which decrease the probability of optimal alignment for covalent binding between the interacting moieties in the bimolecular transition-state complex. Noncovalent intercalation of (+)-anti-BPDE prior to the covalent binding reaction is not a relevant process in the case of single-stranded oligonucleotides and is therefore not a critical requirement for obtaining high yields of covalent trans- and cis-(+)-anti-BPDE-N2-dG adducts in these oligonucleotide sequences.

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Section: Discussionmentioning

confidence: 99%

Base-sequence dependence of covalent binding of benzo[a]pyrenediol epoxide to guanine in oligodeoxyribonucleotides

Margulis

Ibáñez

Geacintov³

1993

Chem. Res. Toxicol.

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“…[8][9][10] The first term ofthis formula represents the electrostatic energy, calculated as a sum of interactions between atomic monopoles Q,, obtained from a specially reparameterized Huckel-Del Re procedure (11,12) and damped by a dielectric function E(R) having a sigmoidal form, based on that developed by Hingerty et al (13). We have reformulated this function as shown below so that it is possible to vary both the plateau value of the dielectric reached at long distance (D) and the slope of the sigmoidal segment of the function (S).…”

Section: Methodsmentioning

confidence: 99%

Energetic coupling between DNA bending and base pair opening.

Ramstein

Lavery

1988

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

307

222

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The pathway for base pair opening within a B-DNA duplex is investigated by theoretical molecular modeling. The results show that the disruption of a single base pair is energetically compatible with the deductions made from hydrogen exchange measurements. In addition, it is found that the opening process is greatly facilitated by DNA bending and that, conversely, once a base pair is disrupted, DNA can bend very easily. It appears that the energetic coupling between these two processes may play an important role in many biological reactions involving nucleic acid distortion. Despite the accumulation of a wealth of information leading to a better knowledge of the chemical mechanism and of the corresponding time range (1-4), the conformational and energetic details of the pathway for opening and the effect of changes in the tertiary structure of DNA remain unclear. Most notably, the mechanism by which a given base pair manages to accumulate enough energy to spontaneously open and disrupt its hydrogen bonds is still fully unknown. These questions are addressed here by theoretical calculations on a B-DNA oligomer. Using the JUMNA (junction minimization of nucleic acids) molecular modeling program (5), we study the energetics and the conformational route for opening one base within a short DNA fragment and then demonstrate how base pair opening and bending of the DNA double helix are related to one another. METHODSAll of the conformational energy calculations presently described were carried out by using the FLEX parameterization (6, 7) developed over several years in our laboratory and already exploited in a large number of studies of nucleic acids and other biological molecules (see, for example, refs. 8-10). The calculations described here were performed under dielectric damping conditions corresponding to aqueous solution (S = 0.16, D = 78). The next three energy terms represent dispersion-repulsion interactions calculated with a 6-12 dependence using, in part, the parameter set developed by Zhurkin et al. (14). Hydrogen bonds (HB) are dealt with by the latter two of these terms, which take into account their angular dependence. All of these terms are summed over pairs of atoms separated by at least three chemical bonds.The last two terms represent the distortion energy associated with torsion angles T, (including anomeric effects) and valence angles a,-To study the base-opening or bending processes within a DNA fragment it is necessary to have control over the helicoidal parameters describing the position of the bases in space as well as parameters indicating the path of the helical axis so that a given "open" or "bent" state can be maintained while energy optimizing the rest of the DNA conformation. This possibility, which is unavailable in normal molecular mechanics procedures, can be achieved with the recently developed JUMNA procedure (5).The aim of the JUMNA approach is to combine the control over the helicoidal parameters of DNA with the rapidity and ease of treating internal conformation changes, i...

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“…The chemical basis for site-specific modulation of reactivity in differing DNA sequences remains poorly understood. The propensity toward DNA adduction by reactive electrophiles could be modulated by sequence-specific changes in DNA conformation ( , ), electrostatic potential ( , ), or induced conformational changes of the DNA duplex upon binding of reactive electrophiles ( − ). A combination of these effects could well be involved, depending upon the specific electrophile.…”

Section: Introductionmentioning

confidence: 99%

Solution Structure of an Oligodeoxynucleotide Containing the Human N-ras Codon 12 Sequence Refined from ¹H NMR Using Molecular Dynamics Restrained by Nuclear Overhauser Effects

Zegar

Stone

1996

Chem. Res. Toxicol.

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The structure of d(GGCAGGTGGTG).d(CACCACCTGCC), consisting of codons 11, 12 (underlined), and 13 of the human n-ras protooncogene, was refined from 1H NMR data. Patterns of internucleotide NOEs consistent with a B-form helix were observed for each strand. NOE intensities between purine H8 and H1' protons were small compared to intensities between cytosine H5 and H6 protons, indicative of glycosyl torsion angles in the anti range. Cross-peaks were observed between purine H8 and pyrimidine H5 and CH3 protons on adjacent bases in the direction of purine (5'-->3')pyrimidine, but not in the direction pyrimidine(5'-->3')purine. Watson-Crick hydrogen bonding between bases was intact. A total of 232 experimental distance restraints were obtained. Of these, 143 were intra-residue restraints and 89 were inter-residue restraints. A restrained molecular dynamics/simulated annealing approach yielded 6 MD structures calculated from a B-form starting structure and 6 MD structures from an A-form starting structure. These refined to an average pairwise rms difference of 0.92 angstrom, with maximum pairwise rmsd of 1.35 angstroms. Accuracy of emergent structures was assessed by relaxation matrix back-calculation. The sixth-root residual index of 7.0 x 10(-2) measured between the refined structures and the NOE intensity data suggested that the former were in reasonable agreement with the NOE data. The refined solution structures were in the B-family. Similar to the human n-ras codon 61 sequence [Feng, B., & Stone, M.P. (1995) Chem. Res. Toxicol. 8, 821-832], the ras12 sequence contained local variations in B-like conformation which did not confer large structural alterations upon the duplex, but perhaps modulated the reactivity of the first as compared to the second guanine in codon 12.

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Sequence Selectivity, a Test of the Nature of the Covalent Adduct Formed Between Benzo[a]pyrene and DNA

Cited by 12 publications

References 24 publications

Base-sequence dependence of covalent binding of benzo[a]pyrenediol epoxide to guanine in oligodeoxyribonucleotides

Base-sequence dependence of covalent binding of benzo[a]pyrenediol epoxide to guanine in oligodeoxyribonucleotides

Energetic coupling between DNA bending and base pair opening.

Solution Structure of an Oligodeoxynucleotide Containing the Human N-ras Codon 12 Sequence Refined from ¹H NMR Using Molecular Dynamics Restrained by Nuclear Overhauser Effects

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Sequence Selectivity, a Test of the Nature of the Covalent Adduct Formed Between Benzo[a]pyrene and DNA

Cited by 12 publications

References 24 publications

Base-sequence dependence of covalent binding of benzo[a]pyrenediol epoxide to guanine in oligodeoxyribonucleotides

Base-sequence dependence of covalent binding of benzo[a]pyrenediol epoxide to guanine in oligodeoxyribonucleotides

Energetic coupling between DNA bending and base pair opening.

Solution Structure of an Oligodeoxynucleotide Containing the Human N-ras Codon 12 Sequence Refined from 1H NMR Using Molecular Dynamics Restrained by Nuclear Overhauser Effects

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Solution Structure of an Oligodeoxynucleotide Containing the Human N-ras Codon 12 Sequence Refined from ¹H NMR Using Molecular Dynamics Restrained by Nuclear Overhauser Effects