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首页> 外文期刊>Biochemistry >Effect of mismatched complementary strands and 5 '-change in sequence context on the thermodynamics and structure of benzo[a]pyrene-modified oligonucleotides
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Effect of mismatched complementary strands and 5 '-change in sequence context on the thermodynamics and structure of benzo[a]pyrene-modified oligonucleotides

机译：错配的互补链和序列背景中的5'改变对苯并[a] py修饰的寡核苷酸的热力学和结构的影响

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Benzo[rr]pyrene (B[a]P) is a well-studied environmental carcinogen that when activated can react with DNA to form four major adducts: (+)-trans-, (-)-trans-, (+)-cis-, and (-)-cis-anti-B[a]P-dG. In this study, two oligonucleotides (5'-dCCATT-G(B[a]P)-CTACC-3' and 5'-dCCATC-G(B[a]P)-CTACC-3') were prepared, each containing the four isomeric adducts, and these were hybridized to either complementary sequences or to sequences containing an A, G, or T opposite the adducted guanine. Thermal melting curves, CD, and UV spectra of each duplex were measured and compared with the unmodified counterpart. The raw and relative thermodynamic measurements were then compared which indicated that differences occur that are both adduct and sequence dependent. These differences were next compared with the in vitro DNA polymerase incorporation data and were found to be strikingly correlated. Most significantly, for all four B[a]P isomers a mismatch of an A across from the adduct resulted in the least amount of relative destabilization, while the Watson-Crick complement C showed the most; in vitro studies showed that A is the preferred base incorporated across from each isomer, while C was incorporated least often. This observed correlation suggests that one factor contributing to misincorporation at an adduct site is the thermodynamic stability of the incorporated base. Structurally, the effect of sequence context and mismatched complementary strands were also compared, suggesting that all adducts tend to intercalate within the helix when they are complemented with a mismatched complementary strand. In addition, the level of this intercalation seems to be both sequence and stereoisomer dependent. [References: 46]
机译：苯并[rr] P（B [a] P）是一种经过充分研究的环境致癌物，其活化后可与DNA反应形成四个主要加合物：（+）-反式，（-）-反式，（+）-顺式和（-）-顺式抗B [a] P-dG。在这项研究中，制备了两个寡核苷酸（5'-dCCATT-G（B [a] P）-CTACC-3'和5'-dCCATC-G（B [a] P）-CTACC-3'），每个寡核苷酸均含有四个异构体加合物，将它们与互补序列或与加成的鸟嘌呤相反的含有A，G或T的序列杂交。测量每个双链体的热熔曲线，CD和UV光谱，并将其与未修饰的对应物进行比较。然后比较原始和相对的热力学测量结果，表明发生的差异既取决于加合物，又取决于序列。接下来，将这些差异与体外DNA聚合酶掺入数据进行比较，发现它们之间具有惊人的相关性。最显着的是，对于所有四个B [a] P异构体，加合物对面的A错配导致相对不稳定程度最小，而Watson-Crick补体C表现最强。体外研究表明，A是从每种异构体跨入的首选碱基，而C的引入频率最低。这种观察到的相关性表明，导致加合物位点错误掺入的一个因素是掺入碱的热力学稳定性。在结构上，还比较了序列背景和错配的互补链的影响，表明当所有加合物与错配的互补链互补时，它们倾向于插入螺旋内。另外，这种插入的水平似乎既取决于序列又取决于立体异构体。 [参考：46]

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