Sequence and stacking dependence of 8-oxoguanine oxidation: Comparison of one-electron vs singlet oxygen mechanisms
Sequence and stacking dependence of 8-oxoguanine oxidation: Comparison of one-electron vs singlet oxygen mechanisms
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DOI：
10.1021/ja991929q
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发表时间：
1999-10-13
影响因子：
15
通讯作者：
Burrows, CJ
中科院分区：
文献类型：
--
作者：
Hickerson, RP;Prat, F;Burrows, CJ
研究了含7，8-二氢-8-氧代鸟嘌呤（8-oxoG）的寡脱氧核苷酸在单电子氧化剂（Ir（IV）、Fe（III）、NiCR/KHSO 5和SO 4-）作用下的氧化反应。以及光化学和热生成的单线态氧。单链和双链寡脱氧核苷酸的氧化程度进行了比较，确认理论电离电位的8-oxoG在不同的序列背景下的双链DNA。与鸟嘌呤一样，堆叠在具有3'相邻G的双链体中的8-oxoG残基比堆叠在其他碱基旁边的那些残基更容易被单电子氧化剂氧化，尽管堆叠的效果对于8-oxoG似乎不如G明显。无论序列如何，8-oxoG总是比四种天然核碱基更容易氧化，即使在存在多个G序列的情况下也是如此。与单线态分子氧的反应，被认为是通过环加成机制进行，显示出很少的序列选择性和7倍高的反应性与单链相比，双链体8-oxoG残基。单电子氧化剂，如Ir（IV）配合物，表现出更温和的3-4倍高的反应性与单链DNA。相比之下，与强氧化剂KHSO 5结合使用的席夫碱络合物[NiCR]（2+）显示出对双链体的氧化比单链8-oxoG的氧化高2倍的偏好，这可能是因为高驱动力和竞争G氧化以通过空穴转移平衡到8-oxoG氧化的可能性。总的来说，这些结果指出了单电子氧化的细微机制差异，但单电子和O-1（2）介导的氧化之间的主要区别。此外，他们建议8-oxoG的重要作用，不仅作为氧化DNA损伤的产物，而且作为进一步氧化的底物。
The oxidation of 7,8-dihydro-8-oxoguanine (8-oxoG)-containing oligodeoxynucleotides has been investigated using a variety of oxidants, including one-electron oxidants (Ir(IV), Fe(III), NiCR/KHSO5, and SO4-.) as well as singlet oxygen, generated both photochemically and thermally. The extents of oxidation in single-stranded and duplex oligodeoxynucleotides are compared, confirming theoretical ionization potentials of 8-oxoG in different sequence contexts in duplex DNA. As with guanine, 8-oxoG residues stacked in a duplex with a 3' neighboring G are more readily oxidized by one-electron oxidants than those stacked next to other bases, although the: effect of stacking appears to be less pronounced for 8-oxoG than for G. Regardless of sequence, 8-oxoG is always more easily oxidized than the four natural nucleobases, even in the presence of multiple G sequences. Reactions with singlet molecular oxygen, thought to proceed through a cycloaddition mechanism, show little sequence selectivity and a 7-fold higher reactivity with single-stranded compared to duplex 8-oxoG residues. One-electron oxidants, such as Ir(IV) complexes, showed a more modest 3-4-fold higher reactivity with single-stranded DNA. In contrast, the Schiff base complex [NiCR](2+), used in conjunction with a strong oxidant, KHSO5, shows a 2-fold preference for oxidation of duplex vs single-stranded 8-oxoG, perhaps because of the high driving force and the possibility for competing G oxidation to equilibrate to 8-oxoG oxidation via hole transfer. Overall, these results point to subtle mechanistic differences in one-electron oxidation but a major distinction between one-electron and O-1(2)-mediated oxidation. Furthermore, they suggest an important role for 8-oxoG, not only as a product of oxidative DNA damage but also as a substrate for further oxidation.