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Modulation of the Properties of Nucleic Acids through Structural Modifications

通过结构修饰调节核酸的性质

基本信息

批准号：
RGPIN-2015-05656
负责人：
Yan, Hongbin
金额：
$ 2.55万
依托单位：
Brock University
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2017
资助国家：
加拿大
起止时间：
2017-01-01 至 2018-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632856
关键词：
Modulation Properties Nucleic Acids through

项目摘要

Nucleic acids are crucial for many fundamental biological processes. They carry genetic information, and transmit it through replication, transcription and translation. These molecules are also recognized for their regulatory roles in many cellular processes. This proposal aims at approaches to introduce unique structural moieties into nucleic acids and consequently, confer properties to these molecules that will further our knowledge on the fundamental biological processes. In this regard, three chemical methods will be investigated. First, a methodology to metabolically label nucleic acids will be explored. This chemistry is based on the inverse Electron Demand Diels-Alder reaction between tetrazine and strained alkenes. It is proposed that a strained alkene moiety will be incorporated into nucleosides and subsequently, incorporated into nucleic acids enzymatically. Upon this incorporation, tetrazine that is covalently linked to a BODIPY fluorophore (non-fluorescent in the form of tetrazine-BODIPY conjugate) will be added, where an inverse Electron Demand Diels-Alder reaction takes place to restore the fluorescence. As such reactions are typically very fast, this chemistry will virtually allow for real-time tracking of cellular processes involving nucleic acids, and importantly, with minimal fluorescent background. Second,

核酸对许多基本的生物过程至关重要。它们携带遗传信息，并通过复制、转录和翻译传递。这些分子也因其在许多细胞过程中的调节作用而被认可。该提案旨在将独特的结构部分引入核酸中，从而赋予这些分子以将进一步促进我们对基本生物过程的了解的性质。在这方面，将研究三种化学方法。首先，将探索代谢标记核酸的方法。这种化学反应是基于四嗪和应变烯烃之间的逆电子需求狄尔斯-阿尔德反应。有人提出，应变烯烃部分将被纳入核苷，随后，纳入核酸酶。在该掺入后，将添加共价连接至BODIPY荧光团的四嗪（以四嗪-BODIPY缀合物的形式为非荧光的），其中发生逆电子需求狄尔斯-阿尔德反应以恢复荧光。由于这种反应通常非常快，这种化学反应实际上将允许实时跟踪涉及核酸的细胞过程，并且重要的是，具有最小的荧光背景。第二、