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Long-range oxidation of guanine by Ru(III) in duplex DNA.
Chem Biol. 1997 May; 4(5):389-400.CB

Abstract

BACKGROUND

Theoretical and experimental studies have demonstrated that 5'-GG-3' sequences in DNA are 'hot spots' for oxidative damage, but few studies have definitively addressed whether oxidative damage to DNA may arise from a distance via long-range charge migration. Towards this end, we have prepared tethered ruthenium (Ru)-oligonucleotide duplexes and used a flash-quench strategy to demonstrate long-range charge transport through the DNA double helix.

RESULTS

DNA assemblies containing a tethered Ru(II) intercalator have been synthesized. Ru(III), generated in situ in the presence of externally bound electron-transfer quenchers, promotes base damage selectively at the 5'-G of a 5'-GG-3' doublet located approximately 37 A from the binding site of the oxidant. In the absence of a guanine doublet, oxidative damage occurs equally at all guanine bases in the strand. Oxidative damage is also observed at long range for guanine in a G.A mismatch but not in a G.T mismatch.

CONCLUSIONS

The present study expands the scope of long-range electron-transfer chemistry in terms of experiments, applications, and possible reactions within the cell. Here we demonstrate oxidative damage to DNA occurring with a high quantum yield over a distance of approximately 37ůsing a ground-state oxidant. These results point to the equilibration of the radical across the DNA duplex to the sites of lowest energy. In addition, this charge migration is sensitive to the intervening pi-stack formed by DNA base pairs and hence may be useful for the detection of mismatches.

Authors+Show Affiliations

Beckman Institute California Institute of Technology Pasadena, CA 91125, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9195873

Citation

Arkin, M R., et al. "Long-range Oxidation of Guanine By Ru(III) in Duplex DNA." Chemistry & Biology, vol. 4, no. 5, 1997, pp. 389-400.
Arkin MR, Stemp ED, Pulver SC, et al. Long-range oxidation of guanine by Ru(III) in duplex DNA. Chem Biol. 1997;4(5):389-400.
Arkin, M. R., Stemp, E. D., Pulver, S. C., & Barton, J. K. (1997). Long-range oxidation of guanine by Ru(III) in duplex DNA. Chemistry & Biology, 4(5), 389-400.
Arkin MR, et al. Long-range Oxidation of Guanine By Ru(III) in Duplex DNA. Chem Biol. 1997;4(5):389-400. PubMed PMID: 9195873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-range oxidation of guanine by Ru(III) in duplex DNA. AU - Arkin,M R, AU - Stemp,E D, AU - Pulver,S C, AU - Barton,J K, PY - 1997/5/1/pubmed PY - 1997/5/1/medline PY - 1997/5/1/entrez SP - 389 EP - 400 JF - Chemistry & biology JO - Chem. Biol. VL - 4 IS - 5 N2 - BACKGROUND: Theoretical and experimental studies have demonstrated that 5'-GG-3' sequences in DNA are 'hot spots' for oxidative damage, but few studies have definitively addressed whether oxidative damage to DNA may arise from a distance via long-range charge migration. Towards this end, we have prepared tethered ruthenium (Ru)-oligonucleotide duplexes and used a flash-quench strategy to demonstrate long-range charge transport through the DNA double helix. RESULTS: DNA assemblies containing a tethered Ru(II) intercalator have been synthesized. Ru(III), generated in situ in the presence of externally bound electron-transfer quenchers, promotes base damage selectively at the 5'-G of a 5'-GG-3' doublet located approximately 37 A from the binding site of the oxidant. In the absence of a guanine doublet, oxidative damage occurs equally at all guanine bases in the strand. Oxidative damage is also observed at long range for guanine in a G.A mismatch but not in a G.T mismatch. CONCLUSIONS: The present study expands the scope of long-range electron-transfer chemistry in terms of experiments, applications, and possible reactions within the cell. Here we demonstrate oxidative damage to DNA occurring with a high quantum yield over a distance of approximately 37ůsing a ground-state oxidant. These results point to the equilibration of the radical across the DNA duplex to the sites of lowest energy. In addition, this charge migration is sensitive to the intervening pi-stack formed by DNA base pairs and hence may be useful for the detection of mismatches. SN - 1074-5521 UR - https://www.unboundmedicine.com/medline/citation/9195873/Long_range_oxidation_of_guanine_by_Ru_III__in_duplex_DNA_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-5521(97)90129-0 DB - PRIME DP - Unbound Medicine ER -