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

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
依托单位国家:
加拿大
项目类别:
Engage Grants Program
财政年份:
2018
资助国家:
加拿大
项目状态:
已结题
起止时间:
2018-01-01 至 2019-12-31

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中文摘要
翻译
以RNA为靶点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的不稳定而变得更加复杂。此外,它经常是一个被忽视的药物**目标,因此,药物发现管道通常不会设计包括它。然而,最近的研究表明,非编码的RNA结构调节细菌的生长、存活和毒力,使其成为诱人的药物靶标。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的系统中的应用仍然受到限制。NMX研究和**解决方案公司为生物技术部门提供基于核磁共振的药物筛选服务。这个项目寻求**发展技能、知识库和基础设施,使NMX能够将他们的服务线扩展到基于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。由于许多因素,RNA被认为是一种很难**工作的分子:制备纯的同质RNA分子和避免**降解例如。为了从事筛选结合RNA的小分子,NMX将与Perreault博士的实验室合作,利用他在基于RNA的研究方面的专业知识。Perreault博士的实验室致力于研究与代谢物结合的核糖开关(RNA受体),因此是微调确定分子与RNA相互作用所需方法的极佳模型。NMXS基于核磁共振的药物筛选技术扩展到基于RNA的靶标,有望吸引新客户,并为他们现有的客户群提供**更全面的服务。
英文摘要
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.
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