FOLDING RNA WITH MODIFIED OLIGONUCLEOTIDES

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中可靠地预测RNA结构，并为靶向RNA的治疗提出先导化合物。深入了解静电相互作用在指导RNA折叠的作用将提供热力学和NMR结构研究的双链体含有isoC-isoG碱基对。通过反义试剂提供Au和GU碱基对的选择性形成的假设将用含有2-硫代尿苷和4-硫代尿苷的寡核苷酸进行测试。将测量与短寡核苷酸和来自小鼠卡氏肺孢子虫的I组核酶的结合。该结果将为促进基于RNA序列信息的治疗方法的发现奠定基础。

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.