Base-sequence dependence of noncovalent complex formation and reactivity of benzo[a]pyrene diol epoxide with polynucleotides

Nicholas Geacintov, Manouchehr Shahbaz, Victor Ibanez, Khadija Moussaoui, Ronald G. Harvey

Research output: Contribution to journalArticle

Abstract

The base-sequence selectivity of the noncovalent binding of (±)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) to a series of synthetic polynucleotides in aqueous solutions (5 mM sodium cacodylate buffer, 20 mM NaCl, pH 7.0, 22°C) was investigated. The magnitude of a red-shifted absorbance at 353 nm, attributed to intercalative complex formation, was utilized to determine values of the association constant Kic. Intercalation in the alternating pyridine-purine polymers poly(dA-dT)·(dA-dT) (Kic = 20 000 M-1), poly(dG-dC)·(dG-dC) (4200 M-1), and poly(dA-dC)·(dG-dT) (9600 M-1) is distinctly favored over intercalation in their nonalternating counterparts poly(dA)·(dT) (780 M-1), poly(dG)·(dC) (1800 M-1), and poly(dA-dG)·(dT-dC) (5400 M-1). Methylation at the 5-position of cytosine gives rise to a significant enhancement of intercalative binding, and Kic is 22 000 M-1 in poly(dG-m5dG)·(dG-m5dC). In a number of these polynucleotides, values of Kic for pyrene qualitatively follow those exhibited by BPDE, suggesting that the pyrenyl residue in BPDE is a primary factor in determining the extent of intercalation. Both BPDE and pyrene exhibit a distinct preference for intercalating within dA-dT and dG-m5dC sequences. The catalysis of the chemical reactions of BPDE (hydrolysis to tetrols and covalent adduct formation) is enhanced significantly in the presence of each of the polynucleotides studied, particularly in the dG-containing polymers. A model in which catalysis is mediated by physical complex formation accounts well for the experimentally observed enhancement in reaction rates of BPDE in the alternating polynucleotides; however, in the nonalternating polymers a different or more complex catalysis mechanism may be operative. Finally, complex formation and catalysis at different binding sites are related to the level of covalent binding, one of the critical factors in the expression of the mutagenic and tumorigenic potentials of BPDE and related compounds in cells.

Original languageEnglish (US)
Pages (from-to)8380-8387
Number of pages8
JournalBiochemistry
Volume27
Issue number22
StatePublished - 1988

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7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Polynucleotides
Benzo(a)pyrene
Epoxy Compounds
Poly dA-dT
Catalysis
Intercalation
Polymers
Cacodylic Acid
Methylation
Cytosine
Reaction rates
Chemical reactions
Hydrolysis
Buffers
Sodium
Binding Sites
Association reactions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Base-sequence dependence of noncovalent complex formation and reactivity of benzo[a]pyrene diol epoxide with polynucleotides. / Geacintov, Nicholas; Shahbaz, Manouchehr; Ibanez, Victor; Moussaoui, Khadija; Harvey, Ronald G.

In: Biochemistry, Vol. 27, No. 22, 1988, p. 8380-8387.

Research output: Contribution to journalArticle

Geacintov, Nicholas ; Shahbaz, Manouchehr ; Ibanez, Victor ; Moussaoui, Khadija ; Harvey, Ronald G. / Base-sequence dependence of noncovalent complex formation and reactivity of benzo[a]pyrene diol epoxide with polynucleotides. In: Biochemistry. 1988 ; Vol. 27, No. 22. pp. 8380-8387.
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AU - Shahbaz, Manouchehr

AU - Ibanez, Victor

AU - Moussaoui, Khadija

AU - Harvey, Ronald G.

PY - 1988

Y1 - 1988

N2 - The base-sequence selectivity of the noncovalent binding of (±)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) to a series of synthetic polynucleotides in aqueous solutions (5 mM sodium cacodylate buffer, 20 mM NaCl, pH 7.0, 22°C) was investigated. The magnitude of a red-shifted absorbance at 353 nm, attributed to intercalative complex formation, was utilized to determine values of the association constant Kic. Intercalation in the alternating pyridine-purine polymers poly(dA-dT)·(dA-dT) (Kic = 20 000 M-1), poly(dG-dC)·(dG-dC) (4200 M-1), and poly(dA-dC)·(dG-dT) (9600 M-1) is distinctly favored over intercalation in their nonalternating counterparts poly(dA)·(dT) (780 M-1), poly(dG)·(dC) (1800 M-1), and poly(dA-dG)·(dT-dC) (5400 M-1). Methylation at the 5-position of cytosine gives rise to a significant enhancement of intercalative binding, and Kic is 22 000 M-1 in poly(dG-m5dG)·(dG-m5dC). In a number of these polynucleotides, values of Kic for pyrene qualitatively follow those exhibited by BPDE, suggesting that the pyrenyl residue in BPDE is a primary factor in determining the extent of intercalation. Both BPDE and pyrene exhibit a distinct preference for intercalating within dA-dT and dG-m5dC sequences. The catalysis of the chemical reactions of BPDE (hydrolysis to tetrols and covalent adduct formation) is enhanced significantly in the presence of each of the polynucleotides studied, particularly in the dG-containing polymers. A model in which catalysis is mediated by physical complex formation accounts well for the experimentally observed enhancement in reaction rates of BPDE in the alternating polynucleotides; however, in the nonalternating polymers a different or more complex catalysis mechanism may be operative. Finally, complex formation and catalysis at different binding sites are related to the level of covalent binding, one of the critical factors in the expression of the mutagenic and tumorigenic potentials of BPDE and related compounds in cells.

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