Aptamers and riboswitches as models to help tune NMR-based screening methods to find small molecules that target RNA

适体和核糖开关作为模型，帮助调整基于 NMR 的筛选方法，以找到靶向 RNA 的小分子

• 批准号: 533439-2018
• 负责人: Perreault, Jonathan
• 金额: $ 1.82万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=661980
• 关键词: Aptamers; riboswitches; models; help; tune

The development of drugs which target RNA is challenging as the difficulty associated with examining**potential drug interactions is compounded by RNAs' instability. Also, it has often been an overlooked drug**target and, as such, drug discovery pipelines are typically not designed to include it. However, it has recently**been shown that non-coding RNA structures regulate bacterial growth, survival and virulence making them a**tempting drug target. NMR based drug screening has become an indispensable tool for pharmaceutical**discovery but is still limited in its application with regards to RNA based systems. NMX Research and**Solutions Inc provides NMR based drug screening services to the biotechnology sector. This project seeks to**develop the skills, knowledge base and infrastructure to allow NMX to expand their service line into RNA**based drug discovery. While NMX has several projects for screening of small fragments that bind proteins,**they do not have the expertise to work with RNA. RNA has a reputation of being a molecule very difficult to**work with due to a number of factors: preparation of pure homogenous RNA molecules and avoiding**degradation being to examples. To engage in screening of small molecules binding RNA, NMX will partner**with Dr. Perreault's laboratory to benefit from his expertise in RNA based research. The laboratory of Dr**Perreault works on riboswitches (RNA-receptors) that bind metabolites and are thus excellent models to fine**tune the methodology required to determine interaction of molecules with RNA. The expansion of NMXs'**NMR based drug screening technology into RNA based targets promises to attract new customers and provide**a more comprehensive service for their existing client base.

针对RNA的药物的开发具有挑战性，因为检测潜在药物相互作用的难度与RNA的不稳定性相关联。此外，它经常是一个被忽视的药物靶点，因此，药物发现管道通常不包括它。然而，最近有研究表明，非编码RNA结构调节细菌的生长、生存和毒力，使它们成为诱人的药物靶点。基于核磁共振的药物筛选已经成为药物发现不可或缺的工具，但在基于RNA的系统方面的应用仍然有限。NMX Research and**Solutions Inc .为生物技术行业提供基于NMR的药物筛选服务。该项目旨在开发技能、知识基础和基础设施，使NMX能够将其服务范围扩展到基于RNA的药物发现。虽然NMX有几个筛选结合蛋白质的小片段的项目，但他们没有处理RNA的专业知识。RNA被认为是一种很难处理的分子，原因有很多：制备纯均质RNA分子和避免降解就是例子。为了筛选结合RNA的小分子，NMX将与Perreault博士的实验室合作，从他在RNA研究方面的专业知识中获益。Perreault博士的实验室致力于研究结合代谢物的核糖开关（RNA受体），因此它是精细调整确定分子与RNA相互作用所需的方法的绝佳模型。将nmx的基于NMR的药物筛选技术扩展到基于RNA的靶标有望吸引新客户，并为现有客户群提供更全面的服务。