Studies on RNA Cleavage: Catalyst Design and Mechanism

RNA 切割的研究：催化剂设计和机制

• 批准号: 0415356
• 负责人: Janet Morrow
• 金额: --
• 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: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0415356&HistoricalAwards=false
• 关键词: Studies; RNA; Cleavage; Catalyst; Design

This award by the Inorganic, Bioinorganic and Organometallic Chemistry program supports Professor Janet R. Morrow at the State University of New York at Buffalo to investigate the mechanism of action of a series of mono and dinuclear catalysts of RNA cleavage, which will guide the design of optimal catalysts. The project includes: (1) Characterization of a transition-state analog for phosphodiester cleavage catalyzed by a dinuclear Zn(II) complex to test the hypothesis that the large catalytic effect for these catalyzed reactions results from selectivity in binding of the dianionic reaction transition state at a densely charged cationic catalytic core. (2) Determination of the solvent deuterium isotope effect over a broad range of pH for cleavage of a dinucleoside substrate catalyzed by the dinuclear Zn(II) complex, which will show whether the catalyzed reaction proceeds through a formal proton transfer from an acidic site at the catalyst to the leaving group. (3) The synthesis of new catalysts that incorporate the following design elements. (a) Specificity for binding of nucleosides involving new dinuclear catalysts in which one Zn(II) macrocycle provides binding specificity for a uridine-nucleoside and a second Zn(II)- or Ln(III)- macrocycle acts as the active catalyst of phosphodiester cleavage. (b) Maximization of charge density at a catalytic core of a dinuclear catalyst using a dinuclear Zn(II) complex utilizing a linker alkoxide group that acts to draw the Zn(II) cations together at a catalytic core. The projects on catalysis by lanthanide ions will utilize the new laser facility for lanthanide (Ln) luminescence research at the University of Buffalo (UB), which was established with support from the NSF-MRI program and is expected to foster synergistic interactions and the exchange of ideas. The laser system will also have a positive impact on the training of undergraduate and graduate students at UB, outside graduate universities and at four-year colleges. Experiments that focus on Eu(III) luminescence will be developed and added to the undergraduate curriculum at UB. Interactions are planned with educators at Hunter College, the University of Iowa and Skidmore College that will involve underrepresented minority students from these universities and colleges in projects that utilize this laser.

无机，生物有机和有机金属化学计划的该奖项支持纽约州立大学布法罗州立大学的Janet R. Morrow教授，研究了RNA裂解的一系列单声道和双核催化剂的作用机理，这将指导最佳催化剂设计。 该项目包括：（1）表征通过二核锌（II）复合物催化磷酸二酯裂解的过渡态类似物，以检验以下假设：这些催化反应的较大催化作用是由在密集源自负荷的硫化硫化硫化阳离子型凝固性型蛋白质上的黛兰离子反应状态结合的选择性而产生的。 （2）测定溶剂同位素在pH值范围内的溶剂同位素效应，以裂解由二核锌（II）复合物催化的二核糖苷底物，这将显示催化反应是否通过从催化剂到离开组的酸性部位的正式Proton转移。 （3）合成包含以下设计元素的新催化剂。 （a）涉及新核催化剂的核苷结合的特异性，其中一个Zn（II）大环为尿苷核苷提供了结合特异性，以及第二个Zn（II）或LN（III） - 大环的特异性 - 大环充当磷酸二二酰二二酰二酰二二酰二二酰二酰化的活性催化剂。 （b）利用连接器烷氧化物基团在催化核心上将锌（II）阳离子一起在催化核心一起绘制锌（II）阳离子，使用双核锌（II）络合物在催化催化剂的催化核心处的电荷密度最大化。灯笼离子催化的项目将利用布法罗大学（UB）的新型激光设施（LN）发光研究，该研究是在NSF-MRI计划的支持下建立的，并有望促进协同互动和思想交流。激光系统还将对UB，研究生大学和四年制大学的本科生和研究生的培训产生积极影响。 将开发关注欧盟发光的实验并将其添加到UB的本科课程中。 计划与亨特学院，爱荷华大学和斯基德莫尔学院的教育工作者进行互动，这些教育工作者将涉及这些大学和学院的代表性不足的少数族裔学生，这些学生利用这种激光。