开发一种dna编码文库筛选方法“DEL Zipper”，使rna靶向化学物质的研究成为可能。

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

SLAS Discovery Pub Date : 2024-12-21 DOI:10.1016/j.slasd.2024.100204

Zhongyao Ma , Bin Zou , Jiannan Zhao , Rui Zhang , Qiaoqiao Zhu , Xiaofeng Wang , Linan Xu , Xiang Gao , Xinyue Hu , Wei Feng , Wen Luo , Min Wang , Yunyun He , Zhifeng Yu , Weiren Cui , Qi Zhang , Letian Kuai , Wenji Su

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引用次数: 0

摘要

迄今为止，由于缺乏可靠的筛选分析，rna靶向化学物质尚处于探索阶段。在这项研究中，我们提出了一种新的rna靶向小分子筛选方法，使用专门的dna编码文库（DEL）。我们的研究结果表明，在各种RNA选择过程中，称为“DEL Zipper”的特殊DEL文库可以显著减少单链DNA-RNA区域相互作用信号。通过对g -四重体进行选择，我们发现了与RNA靶点相互作用的新靶点，并通过结合验证了结果。这项研究表明，“DEL Zipper”方法是一种强大的筛选试验，具有发现不同RNA靶标的小分子配体的潜力。

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Development of a DNA-encoded library screening method “DEL Zipper” to empower the study of RNA-targeted chemical matter

To date, RNA-targeted chemical matter is under explored due to a lack of robust screening assays. In this study, we present a novel RNA-targeted small molecule screening approach using a specialized DNA-encoded library (DEL). Our findings reveal that the specialized DEL library, called “DEL Zipper”, can significantly reduce single-stranded DNA-RNA region interaction signals during various kinds of RNA selection. By performing the selection against both G-quadruplex, we have identified novel hits that interact with RNA targets and the results are validated through binding. This study demonstrates that the “DEL Zipper” method is a robust screening assay that has potential for discovering small molecule ligands for diverse RNA targets.

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来源期刊

SLAS Discovery Chemistry-Analytical Chemistry

CiteScore

7.00

自引率

3.20%

发文量

审稿时长

39 days

期刊介绍： Advancing Life Sciences R&D: SLAS Discovery reports how scientists develop and utilize novel technologies and/or approaches to provide and characterize chemical and biological tools to understand and treat human disease. SLAS Discovery is a peer-reviewed journal that publishes scientific reports that enable and improve target validation, evaluate current drug discovery technologies, provide novel research tools, and incorporate research approaches that enhance depth of knowledge and drug discovery success. SLAS Discovery emphasizes scientific and technical advances in target identification/validation (including chemical probes, RNA silencing, gene editing technologies); biomarker discovery; assay development; virtual, medium- or high-throughput screening (biochemical and biological, biophysical, phenotypic, toxicological, ADME); lead generation/optimization; chemical biology; and informatics (data analysis, image analysis, statistics, bio- and chemo-informatics). Review articles on target biology, new paradigms in drug discovery and advances in drug discovery technologies. SLAS Discovery is of particular interest to those involved in analytical chemistry, applied microbiology, automation, biochemistry, bioengineering, biomedical optics, biotechnology, bioinformatics, cell biology, DNA science and technology, genetics, information technology, medicinal chemistry, molecular biology, natural products chemistry, organic chemistry, pharmacology, spectroscopy, and toxicology. SLAS Discovery is a member of the Committee on Publication Ethics (COPE) and was published previously (1996-2016) as the Journal of Biomolecular Screening (JBS).