Structure-selective RNA Cleavage by Metal Ion Catalysts

这一无机化学、生物无机化学和金属有机化学项目的研究奖支持纽约州立大学布法罗大学的Janet Morrow教授的工作，她研究了单核和双核金属离子催化剂对RNA的结构选择性切割，目的是开发用于RNA结构映射的催化剂，并开发用于与常见核酸二级结构特定相互作用的小分子。首先，制备了Sc(III)和La(III)的单核和双核配合物，并对其作为结构选择性RNA切割催化剂进行了研究。其次，将开发分别与尿苷或胸苷结合的识别剂，这些识别剂分别含有RNA或DNA中的突起、错配或环。这些识别剂是基于带有侧链芳基的锌(II)大环络合物。第三，将锌(II)络合物结合到Sc(III)或Eu(III)催化剂上，并研究含尿苷的RNA在凸起和环中的结构选择性切割。稀土离子络合物及其与核酸的相互作用将用发光光谱进行表征。除了培训研究生和本科生进行多学科研究外，研究培训还将扩展到本科课程，为我们的CASPiE项目创建一个新的实验室模块(教育中真实实践中心)。这个模块将包括监测小分子与DNA结合的研究。Morrow集团将开发和维护一种专门的激光系统，用于直接激发镧系元素的发光，并保持该设施对所有研究人员开放。这其中包括纽约州立大学弗里多尼亚分校的学生和教职员工，他们是我们在研究金属离子络合物与核酸结合方面的合作工作。这项工作将为在体外和细胞培养中研究RNA、蛋白质相互作用和RNA结构提供新的工具，并将是靶向特定RNA结构以控制生物功能的第一步。

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.