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适体序列的四重倾向性分析。

Analysis of quadruplex propensity of aptamer sequences.

作者信息

Cucchiarini Anne, Dobrovolná Michaela, Brázda Václav, Mergny Jean-Louis

机构信息

Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, 91120 Palaiseau, France.

Institute of Biophysics, Czech Academy of Sciences, Královopolská 135, 61200 Brno, Czech Republic.

出版信息

Nucleic Acids Res. 2025 May 10;53(9). doi: 10.1093/nar/gkaf424.

Abstract

Aptamers are short DNA or RNA sequences that can fold into unique three-dimensional structures, enabling them to bind specifically to target molecules with high affinity, similar to antibodies. A distinctive feature of many aptamers is their ability to adopt a G-quadruplex (G4) fold, a four-stranded structure formed by guanine-rich sequences. While G4 formation has been proposed or demonstrated for some aptamers, we aimed to investigate how frequently quadruplex-prone motifs emerge from the SELEX process. To achieve this, we examined quadruplex candidate sequences from the UTexas Aptamer Database, which contains over 1400 aptamer sequences extracted from 400 publications spanning several decades. We analyzed the G4 and i-motif propensity of these sequences. While no likely i-motif forming candidates were found, nearly 1/4 of DNA aptamers and 1/6 of RNA aptamers were predicted to form G4 structures. Interestingly, many motifs capable of forming G4 structures were not previously reported or suspected. Out of 311 sequences containing a potential stable G4 motif, only 53 of them (17%) reported the word "quadruplex" in the corresponding article. We experimentally tested G4 formation for 30 aptamer sequences and were able to confirm G4 formation for all the sequences with a G4Hunter score of 1.31 or more. These observations suggest the need to reevaluate G4 propensity among aptamer sequences.

摘要

适体是短的DNA或RNA序列,它们可以折叠成独特的三维结构,使其能够以高亲和力特异性结合靶分子,类似于抗体。许多适体的一个显著特征是它们能够形成G-四链体(G4)折叠,这是一种由富含鸟嘌呤的序列形成的四链结构。虽然已经有人提出或证明了某些适体能够形成G4,但我们旨在研究在指数富集的配体系统进化技术(SELEX)过程中,易于形成四链体的基序出现的频率有多高。为了实现这一目标,我们检查了来自德克萨斯大学适体数据库中的四链体候选序列,该数据库包含从跨越几十年的400篇出版物中提取的1400多个适体序列。我们分析了这些序列形成G4和i-基序的倾向。虽然没有发现可能形成i-基序的候选序列,但预计近1/4的DNA适体和1/6的RNA适体能够形成G4结构。有趣的是,许多能够形成G4结构的基序此前并未被报道或怀疑。在311个包含潜在稳定G4基序的序列中,只有53个(17%)在相应文章中提到了“四链体”一词。我们对30个适体序列进行了G4形成的实验测试,并且能够确认所有G4Hunter分数为1.31或更高的序列都能形成G4。这些观察结果表明有必要重新评估适体序列中形成G4的倾向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f9/12082452/b858a4366c82/gkaf424figgra1.jpg

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