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DNA alkylation promoted by an electron-rich quinone methide intermediate

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Abstract

Biological application of conjugates derived from oligonucleotides and quinone methides have previously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substituent has been placed para to the nascent exo-methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5'-aminohexyloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA

    Chengyun Huang & Steven E. Rokita

  2. Sichuan Institute of Geological Engineering Investigation, Chengdu, 610072, China

    Chengyun Huang

  3. Department of Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA

    Steven E. Rokita

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  1. Chengyun Huang
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  2. Steven E. Rokita
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Correspondence to Steven E. Rokita.

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Huang, C., Rokita, S.E. DNA alkylation promoted by an electron-rich quinone methide intermediate. Front. Chem. Sci. Eng. 10, 213–221 (2016). https://doi.org/10.1007/s11705-015-1541-3

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  • DOI: https://doi.org/10.1007/s11705-015-1541-3

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