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Characteristics of Noncovalent and Covalent Interactions of (+) and (-) Anti-Benzo[a]Pyrene Diol Epoxide Stereoisomers of Different Biological Activities with DNA

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Molecular Basis of Specificity in Nucleic Acid-Drug Interactions

Part of the book series: The Jerusalem Symposia on Quantum Chemistry and Biochemistry ((JSQC,volume 23))

Abstract

The (+) and (-) enantiomers of anti-7,8-dio1-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) are characterized by striking differences in their tumorigenic and mutagenic activities. The covalent binding of these isomers leads to DNA adducts with different distributions of conformations. The adducts derived from (+)-BPDE cause significant unwinding of supercoiled DNA, while those derived from (-)-BPDE do not. The conformations of these covalent lesions are different from those of classical intercalation complexes and include external binding modes and adducts which exhibit some though not all characteristics of intercalative binding. New insights into these different adducts are obtained from studies of oligonucleotides of defined base composition and sequence modified covalently at the exocyclic amino group of guanine by cis and trans addition of (+)-BPDE and (-)-BPDE.

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Author information

Authors and Affiliations

  1. Chemistry Department, New York University, New York, NY, 10003, USA

    N. E. Geacintov, M. Cosman, V. Ibanez & S. S. Birke

  2. Radiation Biochemistry Department, Armed Forces Radiobiology Research Institute, Bethesda, MD, 20814, USA

    C. E. Swenberg

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  1. N. E. Geacintov
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  2. M. Cosman
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  3. V. Ibanez
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  4. S. S. Birke
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  5. C. E. Swenberg
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Editor information

Editors and Affiliations

  1. Institut de Biologie Physico-Chimique (Fondation Edmond de Rothschild), Paris, France

    Bernard Pullman

  2. Department of Chemistry, University of Tel-Aviv, Israel

    Joshua Jortner

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Geacintov, N.E., Cosman, M., Ibanez, V., Birke, S.S., Swenberg, C.E. (1990). Characteristics of Noncovalent and Covalent Interactions of (+) and (-) Anti-Benzo[a]Pyrene Diol Epoxide Stereoisomers of Different Biological Activities with DNA. In: Pullman, B., Jortner, J. (eds) Molecular Basis of Specificity in Nucleic Acid-Drug Interactions. The Jerusalem Symposia on Quantum Chemistry and Biochemistry, vol 23. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3728-7_29

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  • DOI: https://doi.org/10.1007/978-94-011-3728-7_29

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