- 期刊
去氧核醣核酸的切割試劑與辨識系統
The Chemistry of DNA-Binding and Cleavage Agents
摘要
去氧核醣核酸(DNA)分子在生物體中扮演訊息儲存與傳遞的角色。基於核酸分子在生物體內的重要角色，由巨分子本身所呈現出的物性及化性，來設計出具備辨識或裂解特定的遺傳訊息之分子，是十分重要的工作，這篇回顧性的文章，將由一些含氧自由基及活性中間體著手，探究其裂解去氧核醣核酸的反應機制，再就國內外研究學者的重要研究成果，從目前所知的理論中，討論近幾年來各種新型態切割試劑的發展；最後，再就核酸本身鹼基排列所形成的序列模組，探討最近在辨識分子的研究趨勢。不僅可使我們對於核酸在生物體內，對活性氧化中間體及自由基的破壞，有更深入的認識，並可提供我們在生物巨分子結構及功能力相關資訊，並彼此交互作用的分析上具備更多樣性的認知，更甚皷，將在未來，有潛力成為以基因為標的新型態藥物，當科學研究漸漸朝向跨領域、著重實用性的趨勢下，這方面的研究，的確值得仔細的玩味。
並列摘要
DNA molecules located in the nucleus of a cell are responsible for the storage and transcription of the genetic message of living organisms. On the basis of our understanding of the physical and chemical properties of DNA, it is now possible for chemists to design reagents that will bind to DNA to prohibit recognition or targeting by pathogenic molecules, or artificial endonucleases that will bind and cleave the DNA. Unlike biological endonucleases, which operate by ＂acid-base＂ chemistry, the chemical endonucleases cut DNA by the activation and formation of free radicals or other reactive intermediates from precursors that are introduced by rational design in the reagents. In this review, I will discuss the oxidative damage of the deoxyribonucleic acids by active free radicals and other reactive intermediates. Based on this chemistry and the known chemical and conformational properties of DNA, a diverse spectrum of novel chemical nucleases have been invented and explored. More recently, modular discrimination systems for the sequential arrangement of the nucleic acid bases have also been reported. By the incorporation of these DNA discrimination systems, e.g., intercalators, major -groove and minor-groove binders, into the DNA binder, DNA cleavage agents can mimic the behavior of cellular endonucleases and could be used to cleave DNA sequences with high specificity. More importantly, these analytical methods as well as the novel technologies that have emerged from these developments have improved our understanding on how biological molecules interact with DNA in general. Finally, the conception of modular designed molecules opens up an approach to the molecular engineering of DNA for genetic manipulation and gene therapy in biomedicine during the 21^(st) century.