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.

Benzo[a]pyrene (BP) is an environmental genotoxin, which, following metabolic activation to 7,8-diol 9,10-epoxide (BPDE) derivatives, forms covalent adducts with cellular DNA. A major fraction of adducts are derived from the binding of N2 of guanine to the C10 position of BPDE. The mutagenic and carcinogenic potentials of these adducts are strongly dependent on the chirality at the four asymmetric benzylic carbon atoms. We report below on the combined NMR-energy minimization refinement characterization of the solution conformation of (-)-trans-anti-[BP]G positioned opposite C and flanked by G.C base pairs in the d(C1-C2-A3-T4-C5-[BP]G6-C7-T8-A9-C10-C11).d(G12-G13-T14++ +-A15-G16-C17- G18-A19-T20-G21-G22) duplex. 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. These results establish Watson-Crick base pair alignment at the [BP]G6.C17 modification site, as well as the flanking C5.G18 and C7.G16 pairs within a regular right-handed helix. The solution structure of the (-)-trans-anti-[BP]G.C 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bounds deduced from NOE buildup curves as constraints in energy minimization computations. The BP ring spans both strands of the duplex in the minor groove and is directed toward the 3'-end of the modified strand in the refined structure. One face of the BP ring of [BP]G6 stacks over the C17 residue across from it on the partner strand while the other face is exposed to solvent.(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  D. Patel,et al.  Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[2]  N. Geacintov,et al.  Spectroscopic characteristics and site I/site II classification of cis and trans benzo[a]pyrene diolepoxide enantiomer-guanosine adducts in oligonucleotides and polynucleotides. , 1991, Carcinogenesis.

[3]  U. Singh,et al.  Structures of the (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyre ne adducts to guanine-N2 in a duplex dodecamer. , 1991, Cancer research.

[4]  N. Geacintov,et al.  Dependence of conformations of benzo[a]pyrene diol epoxide-DNA adducts derived from stereoisomers of different tumorigenicities on base sequence. , 1991, Chemical research in toxicology.

[5]  K. Wilson,et al.  Chirality and its importance in drug development. , 1991, Biochemical Society transactions.

[6]  D. Patel,et al.  NMR studies of the exocyclic 1,N6-ethenodeoxyadenosine adduct (epsilon dA) opposite deoxyguanosine in a DNA duplex. Epsilon dA(syn).dG(anti) pairing at the lesion site. , 1991, Biochemistry.

[7]  J. Seiler.  Chirality-dependent DNA reactivity as the possible cause of the differential mutagenicity of the two components in an enantiomeric pair of epoxides. , 1990, Mutation research.

[8]  N. Geacintov,et al.  Preparation and isolation of adducts in high yield derived from the binding of two benzo[a]pyrene-7,8-dihydroxy-9,10-oxide stereoisomers to the oligonucleotide d(ATATGTATA). , 1990, Carcinogenesis.

[9]  N. Geacintov,et al.  Laser spectroscopic studies of DNA adduct structure types from enantiomeric diol epoxides of benzo[a]pyrene. , 1990, Chemical research in toxicology.

[10]  D. Patel,et al.  NMR and computational characterization of the N-(deoxyguanosin-8-yl)aminofluorene adduct [(AF)G] opposite adenosine in DNA: (AF)G[syn].A[anti] pair formation and its pH dependence. , 1989, Biochemistry.

[11]  J. M. Roman,et al.  DNA adducts from carcinogenic and noncarcinogenic enantiomers of benzo[a]pyrene dihydrodiol epoxide. , 1989, Chemical research in toxicology.

[12]  N. Geacintov,et al.  Linear dichroism properties and orientations of different ultraviolet transition moments of benzo[a]pyrene derivatives bound noncovalently and covalently to DNA. , 1989, Biophysical chemistry.

[13]  T. Hayden,et al.  Prediction of DNA structure from sequence: A build‐up technique , 1989, Biopolymers.

[14]  D. Patel,et al.  NMR studies of exocyclic 1,N2-propanodeoxyguanosine adducts (X) opposite purines in DNA duplexes: protonated X(syn).A(anti) pairing (acidic pH) and X(syn).G(anti) pairing (neutral pH) at the lesion site. , 1989, Biochemistry.

[15]  A. Gräslund,et al.  DNA–carcinogen interaction: covalent DNA-adducts of benzo(a)pyrene 7, 8-dihydrodiol 9, 10-epoxides studied by biochemical and biophysical techniques , 1989, Quarterly Reviews of Biophysics.

[16]  J. Barton.  Targeting DNA sites with chiral metal complexes , 1989 .

[17]  B. Nordén,et al.  Binding geometries of benzo[a]pyrene diol epoxide isomers covalently bound to DNA. Orientational distribution. , 1988, Biochemistry.

[18]  N. Geacintov,et al.  Intercalation and binding of carcinogenic hydrocarbon metabolites to nucleic acids , 1988 .

[19]  B. Reid.  Sequence-specific assignments and their use in NMR studies of DNA structure , 1987, Quarterly Reviews of Biophysics.

[20]  N. Geacintov,et al.  Conformations and selective photodissociation of heterogeneous benzo(a)pyrene diol epoxide enantiomer-DNA adducts. , 1987, Biophysical chemistry.

[21]  D. Patel,et al.  DNA and RNA: NMR studies of conformations and dynamics in solution , 1987, Quarterly Reviews of Biophysics.

[22]  G. Hatch,et al.  Relationships between benzo(a)pyrene-DNA adduct levels and genotoxic effects in mammalian cells. , 1987, Cancer research.

[23]  F. Chen.  Covalent binding of (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyr ene to B and Z DNAs. , 1985, Biochemistry.

[24]  N. Bouck,et al.  Benzo[a]pyrene diol-epoxides: different mutagenic efficiency in human and bacterial cells. , 1985, Mutation research.

[25]  B. Nordén,et al.  Spectroscopic studies of DNA complexes formed after reaction with anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide enantiomers of different carcinogenic potency. , 1984, Carcinogenesis.

[26]  N. Geacintov,et al.  Stereoselective covalent binding of anti-benzo(a)pyrene diol epoxide to DNA conformation of enantiomer adducts. , 1984, Journal of biomolecular structure & dynamics.

[27]  G. Drobny,et al.  Assignment of the non-exchangeable proton resonances of d(C-G-C-G-A-A-T-T-C-G-C-G) using two-dimensional nuclear magnetic resonance methods. , 1983, Journal of molecular biology.

[28]  D. Grunberger,et al.  The correlation between benzo[a]pyrene-induced mutagenicity and DNA adduct formation in Salmonella typhimurium TA100. , 1983, Mutation research.

[29]  S. Nesnow,et al.  Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis. , 1983, Cancer research.

[30]  A. Conney,et al.  Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture. , 1982, Cancer research.

[31]  S. Neidle,et al.  Molecular structure of (+/-)-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene determined by x-ray crystallography. , 1982, Cancer research.

[32]  A. Rich,et al.  Right-handed and left-handed DNA: studies of B- and Z-DNA by using proton nuclear Overhauser effect and P NMR. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[33]  M. Osborne,et al.  Mutation in mammalian cells by stereoisomers of anti-benzo[a] pyrene-diolepoxide in relation to the extent and nature of the DNA reaction products. , 1982, Carcinogenesis.

[34]  K. Straub,et al.  Double-stranded DNA stereoselectively binds benzo(a)pyrene diol epoxides , 1979, Nature.

[35]  T. Slaga,et al.  Marked differences in the skin tumor-initiating activities of the optical enantiomers of the diastereomeric benzo(a)pyrene 7,8-diol-9,10-epoxides. , 1979, Cancer research.

[36]  D. Jerina,et al.  Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D. Jerina,et al.  Binding of benzo[a]pyrene 7,8-diol-9,10-epoxides to DNA, RNA, and protein of mouse skin occurs with high stereoselectivity. , 1978, Science.

[38]  D. Jerina,et al.  Differences in mutagenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides. , 1977, Biochemical and biophysical research communications.

[39]  C. Harris,et al.  Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo. , 1976, Science.