具有化学锁定末端的DNA Aptamers用于病毒感染抑制
Wenzhe Song1, Chuanxi Li2,3, Yuhang Dong1
1State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, 100029, China.
ACS applied materials & interfaces
|March 21, 2025
概括
通过终端的化学交联,可以稳定核酸体对降解的作用. 这种方法增强了阿普坦体的稳定性和功能,对临床应用有希望,例如抑制SARS-CoV-2感染.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 药物开发 药物开发
背景情况:
- 核酸体提供高亲和度和特异性,作为抗体的替代品.
- 胺体的一个主要限制是它们对核酶降解的易感性,这阻碍了生物应用.
研究的目的:
- 开发一种方法来增强亚胺稳定性和核酶抗性.
- 为了研究小分子介导终端操纵对阿普他默稳定性的有效性.
主要方法:
- 设计具有终端T-T基的阿普坦体,用于与三素进行化学交叉链接.
- 合成具有不同终端T-T交联模式的aptamer.
- 采用实验调查和分子动力学模拟来评估交叉链接效率和体稳定性.
- 评估终端锁定型体在抑制SARS-CoV-2感染方面的性能.
主要成果:
- 交叉链接的效率取决于T-T位点的数量,阿巴体构造和竞争性结合.
- 锁定3'和5'末端的阿普塔默显示出显著改善的外核酶抵抗性和向结合.
- 终端锁定的阿普坦体通过向病毒受体结合域,在抑制SARS-CoV-2感染方面表现出卓越的性能.
结论:
- 小分子介导的终端操纵为稳定DNA体提供了一个强大的策略.
- 这种方法增强了对核酶的阿胺耐药性,并保持了目标结合能力.
- 开发的方法具有很大的潜力,可以推进基于核酸的治疗药物的临床应用.
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