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.

这个奖项由无机，生物无机和有机化学计划支持教授珍妮特R。Morrow和布法罗的纽约州立大学的研究人员一起研究了一系列RNA裂解的单核和双核催化剂的作用机制，这将指导最佳催化剂的设计。 该项目包括：（1）表征由双核Zn（II）络合物催化的磷酸二酯裂解的过渡态类似物，以测试以下假设：这些催化反应的大催化效应是由双阴离子反应过渡态在密集带电的阳离子催化核心处结合的选择性引起的。 (2)测定在宽pH范围内的溶剂氘同位素效应，用于由双核Zn（II）络合物催化的二核苷底物的裂解，这将显示催化反应是否通过从催化剂处的酸性位点到离去基团的形式质子转移进行。(3)合成新的催化剂，包括以下设计元素。(a)涉及新的双核催化剂的核苷结合特异性，其中一个Zn（II）大环提供尿苷-核苷的结合特异性，第二个Zn（II）-或Ln（III）-大环充当磷酸二酯裂解的活性催化剂。(b)使用双核Zn（II）络合物使双核催化剂的催化核处的电荷密度最大化，所述双核Zn（II）络合物利用连接体烷氧基基团，所述连接体烷氧基基团用于将Zn（II）阳离子在催化核处吸引在一起。关于镧系元素离子催化的项目将利用布法罗大学（UB）的新激光设施进行镧系元素（Ln）发光研究，该设施是在国家科学基金-磁共振成像方案的支持下建立的，预计将促进协同互动和思想交流。激光系统还将对UB、研究生院外和四年制学院的本科生和研究生的培训产生积极影响。 专注于Eu（III）发光的实验将被开发并添加到UB的本科课程中。 计划与亨特学院、爱荷华州大学和斯基德莫尔学院的教育工作者进行互动，让这些大学和学院中代表性不足的少数民族学生参与利用这种激光的项目。