通过修改的核酸替代,通过酶性DNA合成促进的Aptamer化学空间的审问
Germain Niogret1,2, Alix Bouvier-Müller1, Chiara Figazzolo1
1Institut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France.
Chembiochem : a European journal of chemical biology
|October 14, 2023
概括
选择后 (后SELEX) 化学修饰的体可以使用与古巴生物异构体的酶合成来简化. 这种多用途的方法可以识别出具有维持目标结合的新胺序列,尽管特异性可能会下降.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药用化学 医学化学
背景情况:
- 亚体的化学修饰提高了它们在生物环境中的稳定性和性能.
- 修改可以在选择期间 (mod-SELEX) 或之后 (post-SELEX) 发生.
- 在SELEX后的修改可能需要合成要求.
研究的目的:
- 为了降低后SELEX的aptamer修改的复杂性和工作量.
- 评估一种新的方法,将酶合成与含古巴原核酸结合起来.
- 改进先前已识别的化学修饰的体.
主要方法:
- 利用酶合成进行核酸结合.
- 使用的核酸含有生物异构体或替代的古巴分子.
- 将该方法应用于之前报告的一种针对PvLDH的化学修饰的阿巴.
主要成果:
- 成功识别了一种额外的阿普坦酶序列,该序列与PvLDH标蛋白保持结合.
- 观察到对新发现的aptamer的特异性减少.
- 证明生物异构体不增强化学修饰的体的效力,与小分子药物不同.
结论:
- 开发的多功能方法简化了SELEX后的阿普坦尔修饰.
- 这种方法适用于其他亚和功能性核酸.
- 古巴生物异构剂提供了一条通往修改后的体的途径,但并不能普遍改善功效.
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