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用小分子准RNA三级结构的高通量竞争性结合试验:适用于伪结和G四重复
Sophie E L Wintermans1, Jana S Hoffmann1, Victor van Kuijk1
1Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Nucleic acids research
|August 30, 2025
概括
一种新的测试识别了向复杂RNA结构的分子,如伪结和G-四重复. 这种高吞吐量方法对细菌核糖转换器和病毒RNA进行了验证,有助于发现新的向RNA的配体.
科学领域:
- 生物化学
- 分子生物学
- 药物发现
背景情况:
- 识别与复杂的RNA三级结构结合的小分子 (例如伪结,G四重复) 对于开发新疗法至关重要.
- 现有的选方法往往缺乏复杂RNA标所需的吞吐量或特异性.
研究的目的:
- 开发和验证一种高通量竞争性结合抗意义试验,用于识别RNA三级结构的配体.
- 通过将其应用于细菌核糖转换器和病毒RNA结构来证明试验的多功能性.
主要方法:
- 设计了一种竞争性结合试验,其中潜在的配体与标记的抗意义寡核酸竞争与标记的RNA结构结合.
- 该试验最初是针对PreQ1-I核突交换机伪结进行定制的,并使用已知的配体和类似物进行验证.
- 随后对SARS-CoV-2的G-四重复结构进行了调整,并使用已知的G-四重复配体进行了测试.
主要成果:
- 该测试成功地从图书馆屏幕中识别出针对Fusobacterium nucleatum核糖突变的命中化合物 (4494),该化合物抑制了翻译.
- 虽然发现了污染物, 但它强调了测试的高度敏感性.
- 该测试对SARS-CoV-2的G-四重复结构得到了验证,证明了其广泛适用性.
结论:
- 竞争性结合反感测试是一种敏感和多功能工具,用于发现针对多种RNA三级结构的配体.
- 这种测试扩展了针对RNA的药物发现的可用方法.
- 通过有效选RNA结合分子,这些发现有助于开发新疗法.
相关概念视频
RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
RNA Structure
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
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Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
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