Selective Recognition of Folded RNA by Small Oligomers

目前，作为药物开发的潜在靶点，RNA的利用严重不足：最有可能的原因是缺乏关于如何设计分子来靶向折叠的RNA的基本知识。在我们的研究中，用两个重要的RNA靶标：HIV的TAR RNA和RRE RNA来检测侧链功能化多胺的RNA结合特性。与这些RNA结合的分子可能会阻止病毒的复制。从这项工作中获得的基本知识最终将适用于其他RNA靶标，并将为设计选择性结合折叠RNA结构的分子提供一套通用的指导方针。在过去的一年里，我们建立了一个新的分子库，可以筛选与TAR RNA选择性结合的分子，我们已经使用一些基本的生化方法验证了这一筛选策略。我们仍在优化我们的初始线索，以获得更好的结合亲和力。我们还开始与一个细胞生物学小组合作，研究这些分子在艾滋病毒感染细胞中的活性。此外，我们正在开始与核磁共振光谱仪合作，研究当我们的分子结合时RNA的构象。

Currently, RNA is significantly underutilized as a potential target for drug development: most likely because there exists a lack of basic knowledge about how one should design a molecule to target a folded RNA. In our research, the RNA-binding properties of sidechain-functionalized polyamines are being examined with two important RNA targets: TAR RNA and RRE RNA of HIV. Molecules that bind to these RNAs can potentially shut down replication of the virus. The basic knowledge that will be developed from this work will ultimately be applicable to other RNA targets, and will provide a general set of guidelines for designing molecules that selectively bind a folded RNA structure. Over the past year, we have established a new library of molecules that can be screened for selective binding to TAR RNA, and we have validated this screening strategy using a number of basic biochemical methods. We are still optimizing our initial leads for better binding affinity. We have also initiated a collaboration with a cell biology group to study the activity of these molecules in HIV infected cells. In addition, we are starting a collaboration with NMR spectroscopists to study the conformation of RNA when our molecule binds.