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.

这项研究奖在无机，生物无机和有机化学计划支持珍妮特·莫罗教授在布法罗，州立大学的纽约大学的工作，以检查单核和双核金属离子催化剂的RNA的结构选择性裂解与发展催化剂的RNA结构映射和开发小分子与常见的核酸二级结构的特异性相互作用的目标。 首先，单核和双核配合物的钪（III）和镧系元素（III）将被制备和研究作为结构选择性的RNA裂解催化剂。 其次，将开发分别与RNA或DNA中含有凸起、错配或环的尿苷或胸苷结合的识别剂。 这些识别剂是基于锌（II）大环配合物与连接的侧芳基。 第三，锌（II）络合物粘合剂将拴在钪（III）或铕（III）催化剂和结构选择性切割的RNA含有尿苷在凸起和环将进行研究。 镧系离子复合物及其与核酸的相互作用将通过使用发光光谱来表征。 除了培养研究生和本科生的多学科研究，研究培训将通过创建一个新的实验室模块为我们的CASPiE程序（中心真实的实践教育）扩展到本科课程。 该模块将涉及监测小分子与DNA结合的研究。 Morrow小组将开发和维护一个专门的激光系统，用于直接激发镧系元素发光，并保持该设施对所有研究人员开放。 这包括来自纽约州立大学弗雷多尼亚分校的学生和教职员工，他们与我们合作研究了金属离子络合物与核酸的结合。 这项工作将为体外和细胞培养中RNA蛋白质相互作用和RNA结构的研究提供新的工具，并将成为靶向特定RNA结构以控制生物功能的第一步。