Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA.

  title={Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA.},
  author={Monique Cosman and Carlos R. de los Santos and Radovan Fiala and Brian E. Hingerty and Saty B. Singh and V{\'i}ctor Ib{\'a}{\~n}ez and Leonid A. Margulis and David H. Live and Nicholas E. Geacintov and Suse Broyde},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  pages={1914 - 1918}
We have synthesized, separated, and purified approximately 10 mg of a deoxyundecanucleotide duplex containing a single centrally positioned covalent adduct between (+)-anti-benzo[a]pyrene (BP) diol epoxide and the exocyclic amino group of guanosine. Excellent proton NMR spectra are observed for the (+)-trans-anti-BP diol epoxide-N2-dG adduct positioned opposite dC and flanked by G.C pairs in the d[C1-C2-A3-T4-C5-(BP)G6-C7-T8-A9-C10-C11].d[12- G13-T14-A15-G16-C17-G18-A19-T20-G 21-G22] duplex… Expand
Solution conformation of the (+)-trans-anti-benzo[g]chrysene-dA adduct opposite dT in a DNA duplex.
The results established that the covalently attached benzo[g]chrysene ring intercalates into the DNA helix directed towards the 5'-side of the modified strand and stacks predominantly with dT17 when intercalated between dC5.dT17 base-pair. Expand
Influence of benzo[a]pyrene diol epoxide chirality on solution conformations of DNA covalent adducts: the (-)-trans-anti-[BP]G.C adduct structure and comparison with the (+)-trans-anti-[BP]G.C enantiomer.
Two-dimensional NMR techniques were applied to assign the exchangeable and non-exchangeable protons of the benzo[a]pyrenyl moiety and the nucleic acid in the modified duplex, which establish Watson-Crick base pair alignment at the [BP]G6. Expand
Solution conformation of the (-)-trans-anti-[BP]dG adduct opposite a deletion site in a DNA duplex: intercalation of the covalently attached benzo[a]pyrene into the helix with base displacement of the modified deoxyguanosine into the minor groove.
This work extends the theme of opposite orientations of adducts derived from chiral pairs of (+)- and (-)-anti-BPDE enantiomers to include the aromatic BP ring system, which intercalates into the helix opposite the deletion site, while the modified deoxyguanosine residue is displaced into the minor groove with its face parallel to thehelix axis. Expand
Structural characterization of a (+)-trans-anti-benzo[a]pyrene-DNA adduct using NMR, restrained energy minimization, and molecular dynamics.
A DNA duplex containing a (+)-trans-anti-benzo[a]pyrene adduct covalently attached to the G8 nucleotide in the sequence d(CCTATGT[BP-G]CAC) was synthesized and the structure characterized by one- and two-dimensional NMR spectroscopy, in conjunction with energy minimization and molecular dynamics simulations. Expand
Solution conformation of the (+)-trans-anti-[BPh]dA adduct opposite dT in a DNA duplex: intercalation of the covalently attached benzo[c]phenanthrene to the 5'-side of the adduct site without disruption of the modified base pair.
The structure provides new insights into how a polycyclic aromatic hydrocarbon covalently attached to the major groove edge of deoxyadenosine can still unidirectionally intercalate into the helix without disruption of the modified base pair. Expand
Solution conformation of the (-)-trans-anti-5-methylchrysene-dG adduct opposite dC in a DNA duplex: DNA bending associated with wedging of the methyl group of 5-methylchrysene to the 3'-side of the modification site.
This paper reports on NMR-molecular mechanics structural studies of the (-)-trans-anti-[MC]dG adduct positioned opposite dC in the sequence context of theExpand
Covalent binding of benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxides to DNA: molecular structures, induced mutations and biological consequences.
Two-dimensional NMR in conjunction with energy minimization computation have provided detailed information on the solution structure of single adducts localized in oligonucleotides and Cooperative adduct formation at certain base sequences is suggested by excimer fluorescence. Expand
Solution conformation of the (+)-cis-anti-[BP]dG adduct in a DNA duplex: intercalation of the covalently attached benzo[a]pyrenyl ring into the helix and displacement of the modified deoxyguanosine.
The solution structure of the (+)-cis-anti-[BP]dG-dC 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by upper and lower bounds deduced from NOESY data sets as restraints in energy minimization computations. Expand
Molecular topology of polycyclic aromatic carcinogens determines DNA adduct conformation: a link to tumorigenic activity.
The structural results propose a link between DNA adduct conformation and repair-dependent mutagenic activity, which could ultimately translate into structure-dependent differences in tumorigenic activities. Expand
Mutagenesis studies with four stereoisomeric N2-dG benzo[a]pyrene adducts in the identical 5'-CGC sequence used in NMR studies: G->T mutations dominate in each case.
It is suggested that adduct conformation must be fluid enough in the 5'-CGC sequence that the duplex DNA conformation can interconvert to mutagenic and non-mutagenic conformations during lesion-bypass. Expand