Conformation of d(CpG) modified by the carcinogen 4-aminobiphenyl: a combined experimental and theoretical analysis.
Conformation of d(CpG) modified by the carcinogen 4-aminobiphenyl: a combined experimental and theoretical analysis.
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致癌物 4-氨基联苯修饰的 d(CpG) 构象：实验与理论相结合的分析。
DOI：
10.1021/bi00356a052
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发表时间：
1986
期刊：
影响因子：
2.9
通讯作者：
Hingerty,BE
中科院分区：
文献类型：
--
作者：
Shapiro,R;Underwood,GR;Zawadzka,H;Broyde,S;Hingerty,BE
由反应物质的附着产生的DNA构象的变化可能是决定反应的生物后果的重要因素。我们合成了一种以致癌胺4-氨基联苯为主要加成物的脱氧二核苷单磷酸，并通过理论和实验方法对其构象进行了分析。将d（CpG）与Ar-乙酰氧基-Ar-（三氟乙酰基）-4-氨基联苯反应，得到在鸟嘌呤的C-8处被4-氨基联苯修饰的产物。通过反相高效液相色谱纯化后，获得毫克量的产物。通过圆二色性、质子磁共振和最小势能计算对其进行了分析。显示了具有构象异构体混合物的柔性分子。无论是致癌物质的碱基堆叠状态和碱基-碱基堆叠状态，与鸟嘌呤的顺式和反式，有助于人口的二聚体水平上的混合物。全局最小能量构象有顺鸟嘌呤和致癌物碱基堆积。这种类型的形式计算约占构象异构体总数的58%。由于联苯部分的扭曲性质，致癌物-碱基堆积固有地涉及比平面和刚性三环氨基芴类似物中更少的重叠。这种差异可能与氨基联苯与氨基芴加合物作为鼠伤寒沙门氏菌1538移码诱变剂的有效性降低有关。
The change in DNA conformation produced by the attachment of a reactive substance is likely to be a vital factor in determining the biological consequences of the reaction. We have prepared a deoxydinucleoside monophosphate containing the major adduct derived from the carcinogenic amine 4-aminobiphenyl and analyzed its conformation by theoretical and experimental methods. Reaction of d (CpG) with Ar-acetoxy-Ar-(trifluoroacetyl)-4-aminobiphenyl afforded the product modified at C-8 of guanine with 4-aminobiphenyl. After purification by reverse-phase high-performance liquid chromatography, milligram amounts of product were obtained. It was analyzed by circular dichroism, proton magnetic resonance, and minimized potential-energy calculations. A flexible molecule with a mixture of conformers is indicated. Both carcinogen-base-stacked states and base-base-stacked states, with guanine both syn and anti, contribute to the population mixture on the dimer level. The global minimum-energy conformation has syn-guanine and carcinogen-base stacking. Forms of this type are calculated to represent roughly 58% of the conformer population. Because of the twisted nature of the biphenyl moiety, carcinogen-base stackinginherently involves less overlap than that in the planar and rigid three-ringed aminofluorene analogue. This differencemight relate to the diminished effectiveness of the aminobiphenyl vs. the aminofluorene adduct as a frameshift mutagen in Salmonella typhimurium 1538.