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

Monique Cosman, Carlos De Los Santos, Radovan Fiala, Brian E. Hingerty, Victor Ibanez, Ernestina Luna, Ronald Harvey, Nicholas E. Geacintov, Suse Broyde, Dinshaw J. Patel

Research output: Contribution to journalArticle

Abstract

This paper reports on the solution structure of the (+)-cis-anti-[BP]dG adduct positioned opposite dC in a DNA oligomer duplex which provides the first experimentally based solution structure of an intercalative complex of a polycyclic aromatic hydrocarbon covalently bound to the N2 of deoxyguanosine. The combined NMR-energy minimization computation studies were undertaken on the (+)-cis-anti-[BP]dG adduct embedded in the same d(C5-[BP]G6-C7)·d(G16-C17-G18) trinucleotide segment of the complementary 11-mer duplex studied previously with the stereoisomeric trans adducts. The exchangeable and nonexchangeable protons of the benzo[a]pyrenyl moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. 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. The benzo-[a]pyrene ring of [BP]dG6 is intercalated between intact Watson-Crick dC5·dG18 and dC7·dG16 base pairs in a right-handed DNA helix. The benzylic ring is in the minor groove while the pyrenyl ring stacks with flanking dC5 and dC7 bases on the same strand. The deoxyguanosine ring of [BP]dG6 is not Watson-Crick base paired but displaced into the minor groove with its plane parallel to the helix axis and stacks over the sugar ring of dC5. The dC17 base on the partner strand is displaced from the center of the helix toward the major groove by the intercalated benzo[a]pyrene ring. This intercalative structure of the (+)-cis-anti-[BP]dG·dC 11-mer duplex exhibits several unusually shifted proton resonances which can be readily accounted for by the ring current contributions of the deoxyguanosine and pyrenyl rings of the [BP]dG6 adduct. Several phosphorus resonances are shifted to low and high field of the unperturbed phosphorus spectral region and have been assigned to internucleotide phosphates centered about the [BP]dG6 modification site. These studies define the changes in the helix at the central trinucleotide segment needed to generate the intercalation site for the covalently bound (+)-cis-anti-[BP]dG adduct. Our structural studies to date permit the classification of [BP]dG adducts positioned opposite dC in DNA helices as either site II solvent-exposed structures with intact [BP]dG·dC Watson-Crick pairing as observed for the (+)-trans-anti-[BP]dG adduct [Cosman et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918] and (-)-trans-anti-[BP]dG adduct [De los Santos et al. (1992) Biochemistry 31, 5245-5252] or site I intercalative structures in which the deoxyguanosine ring of [BP]dG and dC are displaced into opposite grooves and the benzo[a]pyrene ring intercalates into the helix as observed for the (+)-cis-anti-[BP]dG adduct in this study.

Original languageEnglish (US)
Pages (from-to)4145-4155
Number of pages11
JournalBiochemistry
Volume32
Issue number16
StatePublished - 1993

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Deoxyguanosine
Intercalation
Conformations
Protons
Benzo(a)pyrene
DNA
Phosphorus
Nuclear magnetic resonance
Biochemistry
Polycyclic Aromatic Hydrocarbons
Oligomers
Sugars
Base Pairing
Nucleic Acids
Phosphates
Datasets

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Cosman, Monique; De Los Santos, Carlos; Fiala, Radovan; Hingerty, Brian E.; Ibanez, Victor; Luna, Ernestina; Harvey, Ronald; Geacintov, Nicholas E.; Broyde, Suse; Patel, Dinshaw J.

In: Biochemistry, Vol. 32, No. 16, 1993, p. 4145-4155.

Research output: Contribution to journalArticle

Cosman, Monique ; De Los Santos, Carlos ; Fiala, Radovan ; Hingerty, Brian E. ; Ibanez, Victor ; Luna, Ernestina ; Harvey, Ronald ; Geacintov, Nicholas E. ; Broyde, Suse ; Patel, Dinshaw J. / 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. In: Biochemistry. 1993 ; Vol. 32, No. 16. pp. 4145-4155.
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abstract = "This paper reports on the solution structure of the (+)-cis-anti-[BP]dG adduct positioned opposite dC in a DNA oligomer duplex which provides the first experimentally based solution structure of an intercalative complex of a polycyclic aromatic hydrocarbon covalently bound to the N2 of deoxyguanosine. The combined NMR-energy minimization computation studies were undertaken on the (+)-cis-anti-[BP]dG adduct embedded in the same d(C5-[BP]G6-C7)·d(G16-C17-G18) trinucleotide segment of the complementary 11-mer duplex studied previously with the stereoisomeric trans adducts. The exchangeable and nonexchangeable protons of the benzo[a]pyrenyl moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. 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. The benzo-[a]pyrene ring of [BP]dG6 is intercalated between intact Watson-Crick dC5·dG18 and dC7·dG16 base pairs in a right-handed DNA helix. The benzylic ring is in the minor groove while the pyrenyl ring stacks with flanking dC5 and dC7 bases on the same strand. The deoxyguanosine ring of [BP]dG6 is not Watson-Crick base paired but displaced into the minor groove with its plane parallel to the helix axis and stacks over the sugar ring of dC5. The dC17 base on the partner strand is displaced from the center of the helix toward the major groove by the intercalated benzo[a]pyrene ring. This intercalative structure of the (+)-cis-anti-[BP]dG·dC 11-mer duplex exhibits several unusually shifted proton resonances which can be readily accounted for by the ring current contributions of the deoxyguanosine and pyrenyl rings of the [BP]dG6 adduct. Several phosphorus resonances are shifted to low and high field of the unperturbed phosphorus spectral region and have been assigned to internucleotide phosphates centered about the [BP]dG6 modification site. These studies define the changes in the helix at the central trinucleotide segment needed to generate the intercalation site for the covalently bound (+)-cis-anti-[BP]dG adduct. Our structural studies to date permit the classification of [BP]dG adducts positioned opposite dC in DNA helices as either site II solvent-exposed structures with intact [BP]dG·dC Watson-Crick pairing as observed for the (+)-trans-anti-[BP]dG adduct [Cosman et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918] and (-)-trans-anti-[BP]dG adduct [De los Santos et al. (1992) Biochemistry 31, 5245-5252] or site I intercalative structures in which the deoxyguanosine ring of [BP]dG and dC are displaced into opposite grooves and the benzo[a]pyrene ring intercalates into the helix as observed for the (+)-cis-anti-[BP]dG adduct in this study.",
author = "Monique Cosman and {De Los Santos}, Carlos and Radovan Fiala and Hingerty, {Brian E.} and Victor Ibanez and Ernestina Luna and Ronald Harvey and Geacintov, {Nicholas E.} and Suse Broyde and Patel, {Dinshaw J.}",
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TY - JOUR

T1 - Solution conformation of the (+)-cis-anti-[BP]dG adduct in a DNA duplex

T2 - Intercalation of the covalently attached benzo[a]pyrenyl ring into the helix and displacement of the modified deoxyguanosine

AU - Cosman, Monique

AU - De Los Santos, Carlos

AU - Fiala, Radovan

AU - Hingerty, Brian E.

AU - Ibanez, Victor

AU - Luna, Ernestina

AU - Harvey, Ronald

AU - Geacintov, Nicholas E.

AU - Broyde, Suse

AU - Patel, Dinshaw J.

PY - 1993

Y1 - 1993

N2 - This paper reports on the solution structure of the (+)-cis-anti-[BP]dG adduct positioned opposite dC in a DNA oligomer duplex which provides the first experimentally based solution structure of an intercalative complex of a polycyclic aromatic hydrocarbon covalently bound to the N2 of deoxyguanosine. The combined NMR-energy minimization computation studies were undertaken on the (+)-cis-anti-[BP]dG adduct embedded in the same d(C5-[BP]G6-C7)·d(G16-C17-G18) trinucleotide segment of the complementary 11-mer duplex studied previously with the stereoisomeric trans adducts. The exchangeable and nonexchangeable protons of the benzo[a]pyrenyl moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. 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. The benzo-[a]pyrene ring of [BP]dG6 is intercalated between intact Watson-Crick dC5·dG18 and dC7·dG16 base pairs in a right-handed DNA helix. The benzylic ring is in the minor groove while the pyrenyl ring stacks with flanking dC5 and dC7 bases on the same strand. The deoxyguanosine ring of [BP]dG6 is not Watson-Crick base paired but displaced into the minor groove with its plane parallel to the helix axis and stacks over the sugar ring of dC5. The dC17 base on the partner strand is displaced from the center of the helix toward the major groove by the intercalated benzo[a]pyrene ring. This intercalative structure of the (+)-cis-anti-[BP]dG·dC 11-mer duplex exhibits several unusually shifted proton resonances which can be readily accounted for by the ring current contributions of the deoxyguanosine and pyrenyl rings of the [BP]dG6 adduct. Several phosphorus resonances are shifted to low and high field of the unperturbed phosphorus spectral region and have been assigned to internucleotide phosphates centered about the [BP]dG6 modification site. These studies define the changes in the helix at the central trinucleotide segment needed to generate the intercalation site for the covalently bound (+)-cis-anti-[BP]dG adduct. Our structural studies to date permit the classification of [BP]dG adducts positioned opposite dC in DNA helices as either site II solvent-exposed structures with intact [BP]dG·dC Watson-Crick pairing as observed for the (+)-trans-anti-[BP]dG adduct [Cosman et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918] and (-)-trans-anti-[BP]dG adduct [De los Santos et al. (1992) Biochemistry 31, 5245-5252] or site I intercalative structures in which the deoxyguanosine ring of [BP]dG and dC are displaced into opposite grooves and the benzo[a]pyrene ring intercalates into the helix as observed for the (+)-cis-anti-[BP]dG adduct in this study.

AB - This paper reports on the solution structure of the (+)-cis-anti-[BP]dG adduct positioned opposite dC in a DNA oligomer duplex which provides the first experimentally based solution structure of an intercalative complex of a polycyclic aromatic hydrocarbon covalently bound to the N2 of deoxyguanosine. The combined NMR-energy minimization computation studies were undertaken on the (+)-cis-anti-[BP]dG adduct embedded in the same d(C5-[BP]G6-C7)·d(G16-C17-G18) trinucleotide segment of the complementary 11-mer duplex studied previously with the stereoisomeric trans adducts. The exchangeable and nonexchangeable protons of the benzo[a]pyrenyl moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. 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. The benzo-[a]pyrene ring of [BP]dG6 is intercalated between intact Watson-Crick dC5·dG18 and dC7·dG16 base pairs in a right-handed DNA helix. The benzylic ring is in the minor groove while the pyrenyl ring stacks with flanking dC5 and dC7 bases on the same strand. The deoxyguanosine ring of [BP]dG6 is not Watson-Crick base paired but displaced into the minor groove with its plane parallel to the helix axis and stacks over the sugar ring of dC5. The dC17 base on the partner strand is displaced from the center of the helix toward the major groove by the intercalated benzo[a]pyrene ring. This intercalative structure of the (+)-cis-anti-[BP]dG·dC 11-mer duplex exhibits several unusually shifted proton resonances which can be readily accounted for by the ring current contributions of the deoxyguanosine and pyrenyl rings of the [BP]dG6 adduct. Several phosphorus resonances are shifted to low and high field of the unperturbed phosphorus spectral region and have been assigned to internucleotide phosphates centered about the [BP]dG6 modification site. These studies define the changes in the helix at the central trinucleotide segment needed to generate the intercalation site for the covalently bound (+)-cis-anti-[BP]dG adduct. Our structural studies to date permit the classification of [BP]dG adducts positioned opposite dC in DNA helices as either site II solvent-exposed structures with intact [BP]dG·dC Watson-Crick pairing as observed for the (+)-trans-anti-[BP]dG adduct [Cosman et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918] and (-)-trans-anti-[BP]dG adduct [De los Santos et al. (1992) Biochemistry 31, 5245-5252] or site I intercalative structures in which the deoxyguanosine ring of [BP]dG and dC are displaced into opposite grooves and the benzo[a]pyrene ring intercalates into the helix as observed for the (+)-cis-anti-[BP]dG adduct in this study.

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JF - Biochemistry

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