FOLDING RNA WITH MODIFIED OLIGONUCLEOTIDES

用修饰寡核苷酸折叠 RNA

• 批准号: 6165473
• 负责人: DOUGLAS H. TURNER
• 金额: $ 3.42万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6165473
• 关键词: RNA; antisense nucleic acid; chemical binding; conformation; intermolecular interaction; ionic bond; nuclear magnetic resonance spectroscopy; nucleic acid sequence; nucleic acid structure; oligonucleotides; ribozymes; structural biology; thermodynamics

The ultimate goals of this research are to characterize the forces directing RNA folding, and to use this knowledge to reliably predict RNA structure from sequence and to suggest lead compounds for therapeutics targeting RNA. Insights into the role of electrostatic interactions in directing RNA folding will be provided by thermodynamic and NMR structural studies of duplexes containing isoC-isoG base pairs. A hypothesis for providing selective formation of AU and GU base pairs by antisense agents will be tested with oligonucleotides containing 2- thiouridine and 4-thiouridine. Binding will be measured to short oligonucleotides and to a group I ribozyme derived from mouse Pneumocystis carinii. The results will lay a foundation for facilitating discovery of therapeutics based on RNA sequence information.

这项研究的最终目标是表征指导 RNA 折叠的力，并利用这些知识从序列可靠地预测 RNA 结构，并为靶向 RNA 的治疗建议先导化合物。通过对含有 isoC-isoG 碱基对的双链体的热力学和 NMR 结构研究，可以深入了解静电相互作用在指导 RNA 折叠中的作用。将用含有2-硫尿苷和4-硫尿苷的寡核苷酸来测试通过反义剂选择性形成AU和GU碱基对的假设。将测量与短寡核苷酸和源自小鼠卡氏肺孢子虫的 I 组核酶的结合。研究结果将为促进基于 RNA 序列信息的疗法的发现奠定基础。