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Influence of Intervening Mismatches on Long-Range Guanine Oxidation in DNA Duplexes

Bhattacharya, Pratip K. and Barton, Jacqueline K. (2001) Influence of Intervening Mismatches on Long-Range Guanine Oxidation in DNA Duplexes. Journal of the American Chemical Society, 123 (36). pp. 8649-8656. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20160208-152036536

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Abstract

A systematic investigation of the efficiency of oxidative damage at guanine residues through long-range charge transport was carried out as a function of intervening base mismatches. A series of DNA oligonucleotides were synthesized that incorporate a ruthenium intercalator linked covalently to the 5‘ terminus of one strand and containing two 5‘-GG-3‘ sites in the complementary strand. Single base mismatches were introduced between the two guanine doublet steps, and the efficiency of transport through the mismatches was determined through measurements of the ratio of oxidative damage at the guanine doublets distal versus proximal to the intercalated ruthenium oxidant. Differing relative extents of guanine oxidation were observed for the different mismatches. The damage ratio of oxidation at the distal versus proximal site for the duplexes containing different mismatches varies in the order GC ∼ GG ∼ GT ∼ GA > AA > CC ∼ TT ∼ CA ∼ CT. For all assemblies, damage found with the Δ-Ru diastereomer was found to be greater than with the Λ-diastereomer. The extent of distal/proximal guanine oxidation in different mismatch-containing duplexes was compared with the helical stability of the duplexes, electrochemical data for intercalator reduction on different mismatch-containing DNA films, and base-pair lifetimes for oligomers containing the different mismatches derived from ^1H NMR measurements of the imino proton exchange rates. While a clear correlation is evident both with helix stability and electrochemical data monitoring reduction of an intercalator through DNA films, damage ratios correlate most closely with base-pair lifetimes. Competitive hole trapping at the mismatch site does not appear to be a key factor governing the efficiency of transport through the mismatch. These results underscore the importance of base dynamics in modulating long-range charge transport through the DNA base-pair stack.


Item Type:Article
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http://dx.doi.org/10.1021/ja010996tDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja010996tPublisherArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2001 American Chemical Society. Received April 19, 2001. Publication Date (Web): August 15, 2001. We are grateful to the National Institute of Health for the financial support of this work. We also thank M. E. Núñez for technical assistance.
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Issue or Number:36
Record Number:CaltechAUTHORS:20160208-152036536
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160208-152036536
Official Citation:Influence of Intervening Mismatches on Long-Range Guanine Oxidation in DNA Duplexes Pratip K. Bhattacharya and Jacqueline K. Barton Journal of the American Chemical Society 2001 123 (36), 8649-8656 DOI: 10.1021/ja010996t
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64315
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:08 Feb 2016 23:36
Last Modified:03 Oct 2019 09:36

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