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Influence of intervening mismatches on long-range guanine oxidation in DNA duplexes.
J Am Chem Soc. 2001 Sep 12; 123(36):8649-56.JA

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 approximately GG approximately GT approximately GA > AA > CC approximately TT approximately CA approximately CT. For all assemblies, damage found with the Delta-Ru diastereomer was found to be greater than with the Lambda-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.

Authors+Show Affiliations

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11535068

Citation

Bhattacharya, P K., and J K. Barton. "Influence of Intervening Mismatches On Long-range Guanine Oxidation in DNA Duplexes." Journal of the American Chemical Society, vol. 123, no. 36, 2001, pp. 8649-56.
Bhattacharya PK, Barton JK. Influence of intervening mismatches on long-range guanine oxidation in DNA duplexes. J Am Chem Soc. 2001;123(36):8649-56.
Bhattacharya, P. K., & Barton, J. K. (2001). Influence of intervening mismatches on long-range guanine oxidation in DNA duplexes. Journal of the American Chemical Society, 123(36), 8649-56.
Bhattacharya PK, Barton JK. Influence of Intervening Mismatches On Long-range Guanine Oxidation in DNA Duplexes. J Am Chem Soc. 2001 Sep 12;123(36):8649-56. PubMed PMID: 11535068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of intervening mismatches on long-range guanine oxidation in DNA duplexes. AU - Bhattacharya,P K, AU - Barton,J K, PY - 2001/9/6/pubmed PY - 2002/1/5/medline PY - 2001/9/6/entrez SP - 8649 EP - 56 JF - Journal of the American Chemical Society JO - J. Am. Chem. Soc. VL - 123 IS - 36 N2 - 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 approximately GG approximately GT approximately GA > AA > CC approximately TT approximately CA approximately CT. For all assemblies, damage found with the Delta-Ru diastereomer was found to be greater than with the Lambda-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. SN - 0002-7863 UR - https://www.unboundmedicine.com/medline/citation/11535068/Influence_of_intervening_mismatches_on_long_range_guanine_oxidation_in_DNA_duplexes_ L2 - https://dx.doi.org/10.1021/ja010996t DB - PRIME DP - Unbound Medicine ER -