Mispairing of a site specific major groove (2S,3S)-N6-(2,3,4-trihydroxybutyl)-2'-deoxyadenosyl DNA Adduct of butadiene diol epoxide with deoxyguanosine: formation of a dA(anti).dG(anti) pairing interaction.
Mispairing of a site specific major groove (2S,3S)-N6-(2,3,4-trihydroxybutyl)-2'-deoxyadenosyl DNA Adduct of butadiene diol epoxide with deoxyguanosine: formation of a dA(anti).dG(anti) pairing interaction.
复制标题
位点特异性主沟 (2S,3S)-N6-(2,3,4-三羟基丁基)-2-脱氧腺苷 DNA 加合物丁二烯二醇环氧化物与脱氧鸟苷的错配：形成 dA(抗).dG(抗)
DOI：
10.1021/tx049772p
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发表时间：
2005
影响因子：
4.1
通讯作者：
Stone,MichaelP
中科院分区：
文献类型：
--
作者：
Scholdberg,TandaceA;Nechev,LubomirV;Merritt,WKeither;Harris,ThomasM;Harris,ConstanceM;Lloyd,RStephen;Stone,MichaelP
将腺嘌呤N6与丁二烯二醇环氧化物（BDE）的烷基化反应生成的（2S，3S）-N6-（2，3，4-三羟基丁基）-2 '-脱氧腺苷（BDT）加合物置于寡脱氧核苷酸5'-d（CGGACXAGAAG）-3 '·5'-d（CTTCTGGTCCG）-3 '互补链中的错配脱氧鸟苷核苷酸的对面。该寡脱氧核苷酸含有人N-ras原癌基因的密码子61（下划线）。BDT加合物位于第61位密码子的第2位，命名为61 S，S-BDT-（61，2）A·G加合物。NMR光谱显示存在两种构象的加合错配双链体。在主要构象中，错配碱基对X6·G17以“面对面”的方式取向，其中修饰的核苷酸X6及其互补物G17都是螺旋内的，并且处于关于糖基键的反构象。X_6 N_1与G_（17）N_1H之间以及X_6 N_6 H与G_（17）O_6之间存在氢键。BDT部分的存在允许形成稳定的A·G错配对。无法确定次要构象的同一性。如果不修复，所得错配对将产生A→C突变，其与该腺嘌呤N6 BDT加合物相关[Carmical，J.R.，内切夫湖N.，哈里斯角，澳-地M.，哈里斯，T. M.，和Lloyd，R. S.（2000）Env.Mol.Mutagen.35，48 - 56]。
The (2S,3S)-N6-(2,3,4-trihydroxybutyl)-2‘-deoxyadenosyl (BDT) adduct arising from alkylation of adenine N6by butadiene diol epoxide (BDE) was placed opposite a mismatched deoxyguanosine nucleotide in the complementary strand of the oligodeoxynucleotide 5‘-d(CGGACXAGAAG)-3‘·5‘-d(CTTCTGGTCCG)-3‘. This oligodeoxynucleotide contains codon 61 (underlined) of the humanN-rasprotooncogene. The BDT adduct was at the second position of codon 61, and this was named theras61S,S-BDT-(61,2) A·G adduct. NMR spectroscopy revealed the presence of two conformations of the adducted mismatched duplex. In the major conformation, the mismatched base pair X6·G17was oriented in a “face-to-face” orientation, in which both the modified nucleotide X6and its complement G17were intrahelical and in the anti conformation about the glycosyl bond. Hydrogen bonding was suggested between X6N1 and G17N1H and between X6N6H and G17O6. The presence of the BDT moiety allowed formation of a stable A·G mismatch pair. The identity of the minor conformation could not be determined. If not repaired, the resulting mismatch pair would generate A→C mutations, which have been associated with this adenine N6BDT adduct [Carmical, J. R., Nechev, L. N., Harris, C. M., Harris, T. M., and Lloyd, R. S. (2000)Env.Mol.Mutagen.35, 48−56].