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

靶向RNA的药物的开发是具有挑战性的，因为与检查潜在药物相互作用相关的困难因RNA的不稳定性而加剧。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，最近的研究表明，非编码RNA结构调节细菌的生长，存活和毒力，使它们成为一个诱人的药物靶点。基于NMR的药物筛选已经成为药物发现的不可或缺的工具，但其在基于RNA的系统中的应用仍然有限。NMX Research和 **Solutions Inc为生物技术部门提供基于NMR的药物筛选服务。该项目旨在 ** 发展技能，知识基础和基础设施，使NMX能够将其服务线扩展到基于RNA** 的药物发现。虽然NMX有几个项目用于筛选结合蛋白质的小片段，但他们没有与RNA合作的专业知识。RNA被认为是一种很难处理的分子，这是由于许多因素造成的：例如，制备纯的同质RNA分子和避免降解。为了从事小分子结合RNA的筛选，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受益。Perreault博士的实验室研究核糖开关（RNA受体），核糖开关结合代谢物，因此是微调确定分子与RNA相互作用所需的方法的极好模型。NMX的基于NMR的药物筛选技术扩展到基于RNA的靶点，有望吸引新客户，并为其现有客户群提供更全面的服务。

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.