RESEARCH ARTICLE

DNA alkylation promoted by an electron-rich quinone methide intermediate

  • Chengyun Huang 1,2 ,
  • Steven E. Rokita , 1,3
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  • 1. Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA
  • 2. Sichuan Institute of Geological Engineering Investigation, Chengdu 610072, China
  • 3. Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA

Received date: 11 Aug 2015

Accepted date: 04 Oct 2015

Published date: 19 May 2016

Copyright

2015 Higher Education Press and Springer-Verlag Berlin Heidelberg

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.

Cite this article

Chengyun Huang , Steven E. Rokita . DNA alkylation promoted by an electron-rich quinone methide intermediate[J]. Frontiers of Chemical Science and Engineering, 2016 , 10(2) : 213 -221 . DOI: 10.1007/s11705-015-1541-3

Acknowledgment

We thank Lyle Isaacs for his suggestions on QMP design and the NIH (CA81571) for partial support of this project. The authors declare no competing financial interests.

Electronic Supplementary Material

ƒSupplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11705-015-1541-3 and is accessible for authorized users.
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