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模板序列和二次结构对DNA模板反应性的影响
Thomas M Snyder1, Brian N Tse, David R Liu
1Howard Hughes Medical Institute and the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Journal of the American Chemical Society
|January 9, 2008
概括
DNA模板合成需要最佳的DNA二次结构,以实现高效的反应. 太多或太少的内部结构阻碍了小分子合成,影响了DNA模板图书馆.
科学领域:
- 生物化学 生物化学
- 有机化学 有机化学
- 分子生物学分子生物学
背景情况:
- DNA模板有机合成允许创建和放大编码合成小分子库的DNA序列.
- 在DNA模板合成中增加库的大小可以导致模板内的分子内配,阻碍反应.
研究的目的:
- 系统地研究DNA模板序列和二次结构对DNA模板反应性的影响.
- 开发用于从DNA模板库中预测和删除有问题的序列的计算方法.
主要方法:
- 计算设计了一系列具有不同程度内部二次结构的DNA模板序列.
- 在DNA模板反应中测试了这些序列的反应性.
- 分析了预测的二次结构,试剂杂交和反应效率之间的关系.
主要成果:
- 在试剂结合部位预测的高水平的二次结构阻碍了杂交并降低了反应性.
- 意想不到的是,具有最小预测二次结构的模板也显示了较差的反应效率.
- 发现中等程度的内部二次结构可以最大限度地提高反应物之间的有效度,可能是通过压缩核酸.
结论:
- 理想的DNA模板序列用于DNA模板合成平衡内部二次结构,避免过多或过少的极端.
- 这些发现表明,有关有效度和干预核酸二次结构的一般原则,可能适用于生物系统.
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