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I 类内含子作为抗真菌化合物的潜在靶标:-剪接高通量筛选策略的开发。

Group I Intron as a Potential Target for Antifungal Compounds: Development of a -Splicing High-Throughput Screening Strategy.

机构信息

Early Discovery, Biochemistry Excellence, Centre de Recherche La Dargoire, Bayer SAS, 69009 Lyon, France.

出版信息

Molecules. 2023 May 31;28(11):4460. doi: 10.3390/molecules28114460.

Abstract

The search for safe and efficient new antifungal compounds for agriculture has led to more efforts in finding new modes of action. This involves the discovery of new molecular targets, including coding and non-coding RNA. Rarely found in plants and animals but present in fungi, group I introns are of interest as their complex tertiary structure may allow selective targeting using small molecules. In this work, we demonstrate that group I introns present in phytopathogenic fungi have a self-splicing activity in vitro that can be adapted in a high-throughput screening to find new antifungal compounds. Ten candidate introns from different filamentous fungi were tested and one group ID intron found in showed high self-splicing efficiency in vitro. We designed the intron to act as a -acting ribozyme and used a fluorescence-based reporter system to monitor its real time splicing activity. Together, these results are opening the way to study the druggability of such introns in crop pathogen and potentially discover small molecules selectively targeting group I introns in future high-throughput screenings.

摘要

为了寻找安全有效的农业用新型抗真菌化合物,人们更加努力地寻找新的作用模式。这涉及到新的分子靶点的发现,包括编码和非编码 RNA。I 组内含子在植物和动物中很少见,但在真菌中存在,由于其复杂的三级结构可能允许使用小分子进行选择性靶向,因此它们具有吸引力。在这项工作中,我们证明了存在于植物病原真菌中的 I 组内含子在体外具有自我剪接活性,可以通过高通量筛选进行适应,以找到新的抗真菌化合物。从不同丝状真菌中测试了 10 个候选内含子,发现一种存在于 的 I 组内含子在体外具有很高的自我剪接效率。我们设计了 内含子作为 -作用核酶,并使用基于荧光的报告系统来监测其实时剪接活性。总之,这些结果为研究作物病原体中此类内含子的可药性开辟了道路,并有可能在未来的高通量筛选中发现选择性靶向 I 组内含子的小分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6428/10254303/99582ddbba40/molecules-28-04460-g001.jpg

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