Evidence for glycosidic bond rotation in a nucleobase peroxyl radical and its effect on tandem lesion formation
Evidence for glycosidic bond rotation in a nucleobase peroxyl radical and its effect on tandem lesion formation
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DOI：
10.1021/jo0492158
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发表时间：
2004-10-15
影响因子：
3.6
通讯作者：
Greenberg, MM
中科院分区：
文献类型：
--
作者：
Hong, IS;Carter, KN;Greenberg, MM
核碱基过氧自由基是生物聚合物在有氧条件下进行γ-辐解时在DNA中形成的主要反应中间体。由5，6-二氢-2 '-脱氧尿苷-6-基衍生的过氧自由基（1）的主要反应途径涉及π键加成或从相邻核苷酸夺取氢原子以产生串联损伤。在DNA的特定位点独立产生1的能力使我们能够通过改变局部DNA结构来探测其反应性。DNA结构变化的影响表明，1反应，从其顺式和反构象的竞争与巯基捕获。这些实验还表明，串联损伤将作为非对映异构体的混合物产生，这可能影响其生物学效应。
Nucleobase peroxyl radicals are the major reactive intermediates formed in DNA when the biopolymer is exposed to gamma-radiolysis under aerobic conditions. The major reaction pathways for the peroxyl radical (1) derived from 5,6-dihydro-2'-deoxyuridin-6-yl involve pi-bond addition to or hydrogen atom abstraction from the adjacent nucleotides to produce tandem lesions. The ability to independently generate 1 at a defined site in DNA enabled us to probe its reactivity by varying the local DNA structure. The effect of DNA structure variation reveals that 1 reacts from its syn- and anti-conformations in competition with trapping by thiol. These experiments also reveal that tandem lesions will be produced as a mixture of diastereomers, which could impact their biological effects.