HYDROLYTIC CLEAVAGE OF RNA BY METAL COMPLEXES, FUNDAMENTAL STUDY IN CATALYSIS

金属配合物对 RNA 的水解裂解，催化基础研究

• 批准号: 6665799
• 负责人: James K. Bashkin
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665799
• 关键词: biological products; biomedical resource; nucleic acids; spectrometry

The destruction of RNA is a process of fundamental biochemical importance, and also has direct bearing on the development of new genomic-based drug strategies. The destruction of RNA is accomplished in this proposal by inorganic catalysts that cleave RNA through transesterification of its phosphodiester backbone. For example, appropriate catalysts are derived from Cu(II)terpyridine, as well as from other complexes of copper, zinc and the lanthanides. Here, the mechanism of RNA cleavage by all of these classes of catalyst will be studied using a new substrate containing a single RNA residue embedded in a DNA polymer. The new substrate is called "embedded RNA", or embRNA. The embRNA substrate maintains the biological relevance of RNA polymers but provides the simplicity and practicality inherent to RNA dimers. EmbRNA furthermore allows highly specific features of RNA-metal binding to be assessed for their importance to the cleavage reaction. These features in clud e charge and hydrophobic effects, remote coordination of metals, and subtle two-metal mechanisms. The work has relevance to development of pharmaceutical reagents to fight viral infections and cancer. The approach is to gain an understanding of the reaction mechanism so that RNA cleavage can be optimized for use in chemotherapy. The mechanistic information gained from this work will feed into separate projects that focus on the sequence-specific cleavage of RNA by ribozyme mimics. Mass spectrometry is used for characterizing these materials.

RNA的破坏是基本生化的过程 重要性，并且还与新的发展有关 基于基因组的药物策略。 RNA的破坏已完成 在这项提案中，无机催化剂将RNA切割 其磷酸二酯骨架的移剂。 例如， 适当的催化剂来自Cu（II）terpyridine，以及 来自铜，锌和灯笼的其他复合物。 在这里， 所有这些类别的催化剂的RNA裂解机制将是 使用包含嵌入单个RNA残基的新底物进行研究 在DNA聚合物中。 新底物称为“嵌入RNA”，或 安娜。 embrna底物保持了生物学相关性 RNA聚合物，但提供了固有的简单性和实用性 RNA二聚体。 Embrna此外允许高度特定的特征 RNA - 金属结合以评估其对裂解的重要性 反应。 这些特征在电荷和疏水作用中， 金属的远程协调和微妙的两级机制。 这 工作与制定药物试剂的开发有关 病毒感染和癌症。 方法是获得理解 反应机制，以便可以优化RNA裂解 用于化学疗法。 从中获得的机械信息 工作将涉足专注于 核酶模拟物对RNA的序列特异性切割。 大量的 光谱法用于表征这些材料。