Oxygen independent DNA interstrand cross-link formation by a nucleotide radical

被引：83

作者：

Hong, IS ^{[1
]}

Ding, H ^{[1
]}

Greenberg, MM ^{[1
]}

机构：

[1] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 02期

关键词：

D O I：

10.1021/ja0563657

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A 5-(2'-Deoxyuridinyl)methyl radical (1) was independently generated from three photochemical precursors and is the first example of a DNA radical that forms interstrand cross-links. Oxygen labeling experiments support generation of 1 by all precursors. Interstrand cross-links are produced upon irradiation of DNA containing any of the precursors. Cross-linking occurs via reaction with the opposing 2'deoxyadenosine and is independent of O-2. The independence of cross-link formation on O-2 is explained by kinetic analysis, which shows that the radical reacts reversibly with O-2. Examination of the effects of glutathione on cross-link formation under anaerobic conditions suggests that adoption of the synconformation by 1 is the rate-limiting step in the process. Interstrand cross-link formation is reversible in the presence of a good nucleophile. The stability of the interstrand cross-link suggests that the isolated molecule is a rearrangement product of that formed in solution. The rearrangement is a consequence of the isolation procedure but also occurs slowly in solution. Oxygen independent cross-link formation may be useful for the purposeful damage of DNA in hypoxic tumor cells, where O-2 is deficient.

引用

页码：485 / 491

页数：7

共 38 条

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