Optochemical control of deoxyoligonucleotide function via a nucleobase-caging approach.
Optochemical control of deoxyoligonucleotide function via a nucleobase-caging approach.
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DOI：
10.1021/ar400036a
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发表时间：
2014-01-21
影响因子：
18.3
通讯作者：
Deiters, Alexander
中科院分区：
文献类型：
--
作者：
Liu, Qingyang;Deiters, Alexander
合成寡核苷酸已被广泛应用于控制广泛的生物过程，如基因表达，基因修复，DNA复制和蛋白质活性。基于通常依赖于沃森-克里克碱基配对相互作用的成熟的序列设计规则，研究人员可以容易地编程这些寡核苷酸的功能。因此，寡核苷酸为靶向广泛的生物分子（包括DNA、RNA和蛋白质）提供了灵活的平台。此外，寡核苷酸是细胞生物学和发育生物学中常用的研究工具。然而，缺乏条件控制方法阻碍了寡核苷酸活性的精确时空调控，这限制了这些试剂在研究复杂生物学问题中的应用。大自然以高水平的空间和时间分辨率控制生物功能，为了阐明生物过程的分子机制，研究人员需要能够以大自然的精度扰动这些过程的工具。光是一种出色的外部调节元件，因为照射可以在空间和时间上轻松控制。因此，研究人员已经开发了几种不同的方法来用光有条件地控制寡核苷酸活性。最通用的策略之一是通过在寡核苷酸上安装和移除光不稳定的笼状基团来进行光化学调控。为了产生可以用光控制核酸功能的开关，化学家将笼状基团引入寡聚体骨架或特定的核碱基上以阻断寡核苷酸功能，直到笼状基团通过曝光而被去除。在这个帐户中，我们专注于应用笼状核碱基的光调控的DNA功能。使用这种方法，我们有光化学激活和失活的基因表达在转录和翻译水平的空间和时间控制。具体而言，我们已经使用笼状三链体形成寡聚体和DNA诱饵来调节转录，并且我们用光激活的反义试剂调节翻译。此外，我们还讨论了通过光照可以触发DNA酶活性、DNA扩增和DNA诱变的策略。最近，我们开发了光激活DNA逻辑运算，这一进展可能为复杂DNA计算的光化学控制奠定基础。
Synthetic oligonucleotides have been extensively applied to control a wide range of biological processes such as gene expression, gene repair, DNA replication, and protein activity. Based on well-established sequence design rules that typically rely on Watson-Crick base pairing interactions researchers can readily program the function of these oligonucleotides. Therefore oligonucleotides provide a flexible platform for targeting a wide range of biological molecules, including DNA, RNA, and proteins. In addition, oligonucleotides are commonly used research tools in cell biology and developmental biology. However, a lack of conditional control methods has hampered the precise spatial and temporal regulation of oligonucleotide activity, which limits the application of these reagents to investigate complex biological questions. Nature controls biological function with a high level of spatial and temporal resolution and in order to elucidate the molecular mechanism of biological processes, researchers need tools that allow for the perturbation of these processes with Nature's precision. Light represents an excellent external regulatory element as irradiation can be easily controlled spatially and temporally. Thus, researchers have developed several different methods to conditionally control oligonucleotide activity with light. One of the most versatile strategies is optochemical regulation through the installation and removal of photo-labile caging groups on oligonucleotides. To produce switches that can control nucleic acid function with light, chemists introduce caging groups into the oligomer backbone or on specific nucleobases to block oligonucleotide function until the caging groups are removed by light exposure. In this Account, we focus on the application of caged nucleobases to the photo-regulation of DNA function. Using this approach we have both optochemically activated and deactivated gene expression at the transcriptional and translational level with spatial and temporal control. Specifically, we have used caged triplex-forming oligomers and DNA decoys to regulate transcription, and we have regulated translation with light-activated antisense agents. Moreover, we also discuss strategies that can trigger DNA enzymatic activity, DNA amplification, and DNA mutagenesis by light illumination. More recently, we have developed light-activated DNA logic operations, an advance that may lay the foundation for the optochemical control of complex DNA calculations.
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影响因子：
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通讯作者：
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影响因子：
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