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Evaluation of RNA cleavage reaction based on the prediction parameters for nucleic acid structures

基于核酸结构预测参数的RNA切割反应评估

基本信息

批准号：
13132208
负责人：
SUGIMOTO Naoki
金额：
$ 28.1万
依托单位：
Konan University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

项目摘要

Toward functionalization of nucleic acids and their uses as a biomaterial, we investigated RNA cleavage reactions based on the prediction parameters for nucleic acid structures. We first carried out determinations of the prediction parameters of nucleic acid conformations and evaluation of the interaction energies. According to our previous results about Watson-Crick and mismatched base pairs, we have determined the thermodynamic parameters for dangling ends and hairpin loop structures which are often found in many ribozymes. Furthermore, important aspects of molecular crowding as well as nucleotide interactions with metal ions and water molecules have also been addressed in this research. On the basis on the quantitative data for the nucleic interactions and structures, we also have successfully constructed polymer receptors for nucleotides, a deoxyribozyme with modified functions, and a molecular sensor that can discriminate an RNA sequence and conformation. In addition, we have designed adenosine derivatives with a flexible linker, and found that the functional DNA containing the artificial nucleoside could interact with nucleotide bases and cleaved a target RNA sequence in the presence of MgCl_2. In summary, our researches guide the prediction of nucleic acid structures, their thermodynamic stability, and design of artificial nucleic acids with functions including ribozymes and artificial nucleotides that act as an artificial nuclease.

为了实现核酸的功能化及其作为生物材料的用途，我们研究了基于核酸结构预测参数的RNA切割反应。我们首先进行了核酸构象预测参数的确定和相互作用能的评估。根据我们以前关于Watson-Crick和错配碱基对的结果，我们确定了许多核酶中常见的悬挂末端和发夹环结构的热力学参数。此外，分子拥挤以及核苷酸与金属离子和水分子的相互作用的重要方面也已在这项研究中得到解决。在此基础上，我们还成功地构建了核苷酸的聚合物受体、功能修饰的脱氧核酶和识别RNA序列和构象的分子传感器。此外，我们还设计了带有柔性连接子的腺苷衍生物，并发现含有人工核苷的功能性DNA在MgCl_2存在下能与核苷酸碱基相互作用并切割靶RNA序列。总之，我们的研究指导了核酸结构的预测，它们的热力学稳定性，以及具有功能的人工核酸的设计，包括作为人工核酸酶的核酶和人工核苷酸。