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.

靶向RNA的药物的开发是具有挑战性的，因为与检查潜在的药物相互作用相关的困难与RNA的不稳定性更加复杂。同样，它通常是一个被忽视的药物**靶标，因此，药物发现管道通常并非旨在包括它。然而，最近**表明，非编码RNA结构调节细菌生长，生存和毒力，使其成为诱人的药物靶标。基于NMR的药物筛查已成为药物**发现的必不可少的工具，但在基于RNA的系统方面的应用仍受到限制。 NMX Research and ** Solutions Inc为生物技术部门提供基于NMR的药物筛查服务。该项目旨在**发展技能，知识库和基础架构，以使NMX能够将其服务线扩展到基于RNA **的药物发现中。虽然NMX有几个用于筛选粘合蛋白质的小片段的项目，但**它们没有专业知识来使用RNA。由于多种因素，RNA的声誉非常难以**：制备纯均匀的RNA分子并避免**降解为示例。为了筛选小分子结合RNA，NMX将与Perreault博士的实验室合作**，从其基于RNA的研究方面受益。 Dr ** perreault的实验室在结合代谢物的核糖开关（RNA受体）上工作，因此是很好的模型，以确定确定分子与RNA相互作用所需的方法。 NMXS的基于NMR的药物筛查技术扩展到基于RNA的目标有望吸引新客户，并为其现有客户群提供更全面的服务。