Synthesis of Site‐Specific Damaged DNA Strands by 8‐(Acetylarylamino)‐2′‐deoxyguanosine Adducts and Effects on Various DNA Polymerases

Synthesis of Site‐Specific Damaged DNA Strands by 8‐(Acetylarylamino)‐2′‐deoxyguanosine Adducts and Effects on Various DNA Polymerases
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8â(乙酰芳基氨基)â2â²â脱氧鸟苷加合物合成位点特异性受损 DNA 链及其对各种 DNA 聚合酶的影响

DOI:
10.1002/ejoc.201200984
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发表时间:
2013
影响因子:
2.8
通讯作者:
C. Meier
C. Meier
中科院分区:
化学3区
文献类型:
--
作者:
S. Krüger;C. Meier

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除了主要发现的8‐(芳基酰胺)‐2′‐dG外,DNA链内的8‐(乙酰芳基酰胺)损伤也可能在化学致癌诱导中起重要作用。利用不同的芳香胺,优化了8‐(乙酰丙基氨基)‐dG加合物的合成途径。8‐修饰的dg被转化为相应的磷酰胺,并位点特异性地结合到不同的寡核苷酸中,从而形成DNA链。这些带有互补寡核苷酸的受损DNA链的杂交体被用来研究它们的熔化特性和圆二色光谱。结果表明,劈裂部位内的损伤没有发生ecori限制。最后,使用三种不同的DNA聚合酶进行引物扩展研究。
Beside the predominately found 8‐(arylamino)‐2′‐dG, 8‐(acetylarylamino) damages within DNA‐strands may also play an important role in the induction of chemical carcinogenesis. A synthesis pathway leading to these 8‐(acetylarylamino)‐dG adducts using different aromatic amines has been optimized. The 8‐modified dGs were converted into the corresponding phosphoramidites and site‐specifically incorporated into different oligonucleotides leading to DNA strands. Lesion‐bearing hybrids of these damaged DNA‐strands with complementary oligonucleotides were used to study their melting properties and their circular dichroism spectra. It was shown that noEcoRIrestriction took place with the damage inside the cleavage site. Finally, three different DNA polymerases were used for primer extension studies.
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