双功能反义寡核苷酸中的修饰核苷酸:探索其抗癌潜力。

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-08-21 DOI:10.1002/cmdc.202500220
Natalia Bartyś, Anna Pasternak, Jolanta Lisowiec-Wąchnicka
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引用次数: 0

摘要

双功能反义寡核苷酸(BASOs)是由两个功能部分组成的剪接开关分子工具,即与目标前信使RNA片段杂交的反义部分和招募剪接因子到该定位的调节部分。目的是验证不同修饰的核苷酸对丙酮酸激酶M1/2基因选择性剪接调控的影响以及BASOs的抗癌潜力。通过实时测量细胞增殖和运动来评估修饰BASOs对癌细胞表型的影响。研究表明,化学修饰可显著提高BASOs的治疗特性,如细胞增殖率降低、癌细胞死亡和运动性降低。作为最有希望的修饰,人们认为存在于BASOs中的β-L-RNA和解锁的核酸不仅具有剪接调节特性,而且具有抗癌作用。这些研究提出了可能用于蛋白质结合寡核苷酸的有效修饰,以提高其治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Modified Nucleotides in Bifunctional Antisense Oligonucleotides: Exploring their Anticancer Potential

Modified Nucleotides in Bifunctional Antisense Oligonucleotides: Exploring their Anticancer Potential

Bifunctional antisense oligonucleotides (BASOs) are splice-switching molecular tools composed of two, functional parts, that is, antisense part that hybridizes to target pre-messenger RNA fragment and regulatory part that recruits splicing factors to that localization. The aim is to verify the influence of variously modified nucleotides on alternative splicing regulation of the pyruvate kinase M1/2 gene and the anticancer potential of BASOs. The effect of modified BASOs on the phenotype of cancer cells is evaluated by real-time measurement of cell proliferation and motility. The studies reveal chemical modifications that significantly increase the therapeutic properties of BASOs as evidenced by decrease in cell proliferation rate, cancer cell death, and reduced motility. As the most promising modifications, it is considered that β-L-RNA and unlocked nucleic acid, present in BASOs, not only show splicing regulatory properties but also anticancer effects. The studies propose efficient modifications that might be used in protein-binding oligonucleotides to improve their therapeutic efficacy.

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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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