FOLDING RNA WITH MODIFIED OLIGONUCLEOTIDES

本研究的最终目标是表征指导RNA折叠的力量，并利用这一知识从序列中可靠地预测RNA结构，并为靶向RNA的治疗提供先导化合物。静电相互作用在指导RNA折叠中的作用将通过包含isoC-isoG碱基对的双链的热力学和核磁共振结构研究提供。我们将用含有2-硫脲和4-硫脲的寡核苷酸来测试反义试剂选择性形成AU和GU碱基对的假设。结合将测量短寡核苷酸和1组核酶来源于小鼠卡氏肺囊虫。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.