Structure-selective RNA Cleavage by Metal Ion Catalysts

金属离子催化剂对 RNA 进行结构选择性切割

• 批准号: 0911375
• 负责人: Janet Morrow
• 金额: $ 47.5万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0911375&HistoricalAwards=false
• 关键词: Structure; selective; RNA; Cleavage; Metal

This research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Janet Morrow at the University at Buffalo, State University of New York, to examine the structure-selective cleavage of RNA by mononuclear and dinuclear metal ion catalysts with the goal of developing catalysts for RNA structure mapping and developing small molecules for specific interaction with common secondary structures of nucleic acids. First, mononuclear and dinuclear complexes of scandium(III) and lanthanides(III) will be prepared and studied as structure-selective RNA cleavage catalysts. Second, recognition agents that bind to uridine or thymidine containing bulges, mismatches or loops in RNA or DNA, respectively, will be developed. These recognition agents are based on zinc(II) macrocyclic complexes with attached pendent aromatic groups. Third, zinc(II) complex binders will be tethered to scandium(III) or europium(III) catalysts and the structure-selective cleavage of RNAs containing uridines in bulges and loops will be studied. Lanthanide ion complexes and their interactions with nucleic acids will be characterized by using luminescence spectroscopy. In addition to training graduate and undergraduate students in multidisciplinary research, research training will be extended to undergraduate courses by the creation of a new laboratory module for our CASPiE program (Center for Authentic Practice in Education). This module will involve studies to monitor binding of small molecules to DNA. The Morrow group will develop and maintain a specialized laser system for the direct excitation of lanthanide luminescence and keep the facility open to all researchers. This includes students and faculty members from the State University of New York at Fredonia for our collaborative work on the study of metal ion complex binding to nucleic acids. This work will provide new tools for the study of RNA protein interactions and RNA structure in vitro and in cell culture and will be a first step towards targeting specific RNA structures to control biological function.

This research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Janet Morrow at the University at Buffalo, State University of New York, to examine the structure-selective cleavage of RNA by mononuclear and dinuclear metal ion catalysts with the goal of developing catalysts for RNA structure mapping and developing small molecules for specific interaction with common secondary structures of nucleic acids. 首先，将准备并作为结构选择性的RNA裂解催化剂来准备并研究扫描群（III）和兰萨尼德（III）（III）的单核和双核复合物。 其次，将开发与尿苷或胸苷含有凸起，RNA或DNA中的环的识别剂。 这些识别剂基于具有附着的吊体芳香族基团的锌（II）大环复合物。 第三，将研究锌（II）复合粘合剂到scandium（iii）或欧洲蛋白酶（III）催化剂，以及将研究含有尿苷和环中含有尿苷的RNA的结构选择性切割。 通过使用发光光谱法来表征灯笼离子复合物及其与核酸的相互作用。 除了培训多学科研究的培训研究生和本科生外，研究培训还将通过为我们的Caspie计划（真正的教育实践中心）创建新的实验室模块来扩展到本科课程。 该模块将涉及监测小分子与DNA的结合的研究。 Morrow小组将开发并维护专门的激光系统，以直接激发灯笼的发光，并向所有研究人员保持该设施。 其中包括纽约州立大学弗雷多尼亚大学的学生和教职员工，以研究金属离子络合物与核酸结合的合作工作。 这项工作将为研究RNA蛋白相互作用和体外和细胞培养的RNA结构提供新的工具，并将成为靶向特定RNA结构控制生物学功能的第一步。