没有的自动合成关尼骨寡核酸
Kacper Skakuj1, Katherine E Bujold1, Chad A Mirkin1
1Department of Chemistry and the International Institute for Nanotechnology , Northwestern University , 2145 Sheridan Road , Evanston , Illinois 60208 , United States.
Journal of the American Chemical Society
|December 17, 2019
概括
一种基于的新型合成方法简化了脱氧核胺 (DNG) 寡核酸的生产. 这种进步为药物开发提供了更安全,更有效的DNG寡核酸合成.
科学领域:
- 化学合成
- 氧核酸的化学成分
- 药物化学
背景情况:
- 传统的脱氧核胺 (DNG) 寡核酸合成依赖于盐和醇等有毒试剂.
- 这些危险的试剂限制了DNG寡核酸生产的可访问性和可扩展性.
- 开发更安全,更有效的合成方法对于推进基于DNG的疗法至关重要.
研究的目的:
- 报告一种新型,温和且具有成本效益的合成脱氧核氨酸 (DNG) 寡核酸的方法.
- 使用自动化寡核酸合成器证明这种新方法的适用性.
- 评估合成的DNG寡核酸的细胞吸收和毒性.
主要方法:
- 使用作为脱氧核胺 (DNG) 寡核酸合成的合试剂.
- 调整合策略为一个MerMade 12自动化寡核酸合成器.
- 合成了各种DNG寡核酸,包括20米尔DNG链和混合DNA-DNG序列.
主要成果:
- 使用基于的方法实现了95%的高合率.
- 成功合成了迄今为止最长的脱氧核氨酸 (DNG) 寡核酸 (20-mer).
- 已证明DNG寡核酸的强烈无助细胞吸收没有明显的毒性.
结论:
- 以为媒介的合成为DNG寡核制剂的传统方法提供了更安全,更容易获得的替代方案.
- 这种方法有助于产生较长的DNG链和混合DNA-DNG序列.
- 增强细胞吸收和低毒性DNG寡核酸支持它们作为治疗剂的潜力.
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