Long-range guanine oxidation in DNA restriction fragments by a triplex-directed naphthalene diimide intercalator.
Long-range guanine oxidation in DNA restriction fragments by a triplex-directed naphthalene diimide intercalator.
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DOI：
10.1021/bi000285s
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发表时间：
2000-04
期刊：
影响因子：
2.9
通讯作者：
M. Núñez;K. T. Noyes;D. Gianolio;L. McLaughlin;J. Barton
中科院分区：
文献类型：
--
作者：
M. Núñez;K. T. Noyes;D. Gianolio;L. McLaughlin;J. Barton
萘二酰亚胺（NDI）是一种强氧化剂，它能与DNA结合，并能通过光活化的电荷传递损伤DNA的5 '-GG-3'位点的5'鸟嘌呤。当NDI共价连接到形成三链体的寡核苷酸的中心并通过嘧啶、嘌呤-嘧啶基序内的三链体形成递送到限制性片段上的特定位点时，NDI可以在每个方向上从结合位点光氧化至少25-38 bp的鸟嘌呤。电荷迁移发生在来自NDI嵌入剂的两个方向上和靶的两条DNA链上，但氧化对三链体的3'侧显著更有效。当NDI和八面体铑嵌入剂直接连接到三链体形成链的5'末端而不是中心时，仅在嵌入位点的紧邻处产生显著量的氧化损伤。考虑到长程电荷传输依赖于DNA堆积，这些结果表明碱基堆积在双链体-三链体结中的三链体区域的5'端被扭曲。通过三链体形成的光氧化损伤的靶向延伸了我们先前的长距离电荷传输的研究，通过一种不需要将光氧化剂共价连接到被探测的DNA的策略，显着更长的DNA序列。此外，氧化损伤的三链体靶向首次提供了氧化剂周围约200 A的基因组电荷转运的典型距离分布。
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.