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Electrochemical Detection of Lesions in DNA

Boal, Amie K. and Barton, Jacqueline K. (2005) Electrochemical Detection of Lesions in DNA. Bioconjugate Chemistry, 16 (2). pp. 312-321. ISSN 1043-1802. doi:10.1021/bc0497362.

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Electrochemical DNA-based sensors that exploit the inherent sensitivity of DNA-mediated charge transport (CT) to base pair stacking perturbations are capable of detecting base pair mismatches and some common base damage products. Here, using DNA-modified gold electrodes, monitoring the electrocatalytic reduction of DNA-bound methylene blue, we examine a wide range of base analogues and DNA damage products. Among those detected are base damage products O4-methyl-thymine, O6-methyl-guanine, 8-oxo-guanine, and 5-hydroxy-cytosine, as well as a therapeutic base, nebularine. The efficiency of DNA-mediated CT is found not to depend on the thermodynamic stability of the helix. However, general trends in how base modifications affect CT efficiency are apparent. Modifications to the hydrogen bonding interface in Watson−Crick base pairs yields a substantial loss in CT efficiency, as does added steric bulk. Base structure modifications that may induce base conformational changes also appear to attenuate CT in DNA as do those that bury hydrophilic groups within the DNA helix. Addition and subtraction of methyl groups that do not disrupt hydrogen bonding interactions do not have a large effect on CT efficiency. This sensitive detection methodology based upon DNA-mediated CT may have utility in diagnostic applications and implicates DNA-mediated CT as a possible damage detection mechanism for DNA repair enzymes.

Item Type:Article
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URLURL TypeDescription
Boal, Amie K.0000-0002-1234-8472
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2005 American Chemical Society. Received November 4, 2004; Revised Manuscript Received January 19, 2005. Publication Date (Web): February 17, 2005. We are grateful to the NIH (GM61077) for their financial support of this research.
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Issue or Number:2
Record Number:CaltechAUTHORS:20160226-120946590
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Official Citation:Electrochemical Detection of Lesions in DNA Amie K. Boal and Jacqueline K. Barton Bioconjugate Chemistry 2005 16 (2), 312-321 DOI: 10.1021/bc0497362
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64805
Deposited By: Melissa Ray
Deposited On:29 Feb 2016 18:47
Last Modified:10 Nov 2021 23:35

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