Selective Recognition of Folded RNA by Small Oligomers

小寡聚体选择性识别折叠 RNA

• 批准号: 7734056
• 负责人: DANIEL H APPELLA
• 金额: $ 25.14万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7734056
• 关键词: Active Sites; Adopted; Affinity; Binding; Biological; Cells; Cellular biology; Class; Collaborations; Development; Future; Goals; Guidelines; HIV; Knowledge; Pharmaceutical Preparations; Polyamines; Property; Proteins; RNA; RNA Binding; RNA Folding; Research; Small RNA; Specificity; Structure; Tars; Toxic effect; Virus; Virus Replication; Work; design; drug development; molecular recognition; protein function; tat Protein; three dimensional structure

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 identified a new version of our molecules that binds extremely well to TAR RNA and blocks association of the tat protein. A collaboration with a cell biology group to study the activity of these molecules in HIV infected cells has demonstrated reasonably good activity. We are continuing to optimize the biological activity of our molecules to minimize toxicity and we are pursuing fundamental studies to understand the molecular recognition properties of our molecules for TAR RNA.

目前，作为药物开发的潜在靶标，RNA的利用明显不足：很可能是因为缺乏关于如何设计分子以折叠RNA为靶标的基本知识。在我们的研究中，侧链功能化多胺的RNA结合特性研究了两个重要的RNA靶点：HIV的TAR RNA和RRE RNA。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靶点，并将为设计选择性结合折叠RNA结构的分子提供一套通用指导方针。在过去的一年里，我们发现了一种新版本的分子，它与TAR RNA结合得非常好，并阻断了该蛋白质的结合。与细胞生物学小组合作研究这些分子在HIV感染细胞中的活性已经证明了相当好的活性。我们正在继续优化我们的分子的生物活性，以尽量减少毒性，我们正在进行基础研究，以了解我们的分子对TAR RNA的分子识别特性。

项目成果

Aziridination of aliphatic alkenes catalyzed by N-heterocyclic carbene copper complexes.

N-杂环卡宾铜配合物催化脂肪族烯烃的氮丙啶化。

• DOI: 10.1021/ol800288b
• 发表时间: 2008
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Xu,Qun;Appella,DanielH
• 通讯作者: Appella,DanielH