title: Long-range guanine oxidation in DNA restriction fragments by a triplex-directed naphthalene diimide intercalator.
abstract: Naphthalene diimide (NDI), a powerful oxidant that binds avidly to DNA by intercalation, is seen to damage the 5' guanine of 5'-GG-3' sites by photoactivated charge transport through DNA. When covalently tethered to the center of a triplex-forming oligonucleotide and delivered by triplex formation within a pyrimidine.purine-pyrimidine motif to a specific site on a restriction fragment, NDI can photooxidize guanine over at least 25-38 bp in each direction from the site of binding. Charge migration occurs in both directions from the NDI intercalator and on both DNA strands of the target, but the oxidation is significantly more efficient to the 3' side of the triplex. NDI and octahedral rhodium intercalators, when tethered directly to the 5' terminus of the triplex-forming strand as opposed to the center, generate significant amounts of oxidative damage only in the immediate vicinity of the intercalation site. Given that long-range charge transport depends on DNA stacking, these results suggest that the base stack is distorted at the 5' end of the triplex region in the duplex-triplex junction. Targeting of photooxidative damage by triplex formation extends our previous studies of long-range charge transport to significantly longer DNA sequences through a strategy that does not require covalent attachment of the photooxidant to the DNA being probed. Moreover, triplex targeting of oxidative damage provides for the first time a typical distance distribution for genomic charge transport of approximately 200 A around the oxidant.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Núñez
authors.forename: K T
authors.initials: KT
authors.lastname: Noyes
authors.forename: D A
authors.initials: DA
authors.lastname: Gianolio
authors.forename: L W
authors.initials: LW
authors.lastname: McLaughlin
authors.forename: J K
authors.initials: JK
authors.lastname: Barton
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D015245:Deoxyribonuclease BamHI / Q000737:chemistry*; D015246:Deoxyribonuclease EcoRI / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D007094:Imides; D007364:Intercalating Agents / Q000737:chemistry*; D008969:Molecular Sequence Data; D009281:Naphthalenes; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry
chemical_list: D007094:Imides; D007364:Intercalating Agents; D009281:Naphthalenes; D009841:Oligonucleotides; D009942:Organometallic Compounds; D010618:Phenanthrolines; C051802:triplex DNA; C062253:bis(phenanthrenequinonediimine)(bipyridyl)rhodium(III); C542131:naphthalenediimide; D015082:2,2'-Dipyridyl; D006147:Guanine; D004247:DNA; D012238:Rhodium; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI