在液相寡核酸合成中调整可溶性支结构的可溶性
Petja Rosenqvist1, Verneri Saari1, Mikko Ora1
1Department of Chemistry, University of Turku, 20500 Turku, Finland.
The Journal of organic chemistry
|September 9, 2024
概括
优化核基保护组可以提高液相寡核酸合成 (LPOS) 中寡核酸可溶性支持结构的溶解性和恢复性. 这一策略改善了寡核酸合成的整体产量和纯度.
科学领域:
- 橄核酸合成的合成方法
- 药用化学 医学化学
- 有机合成 有机合成
背景情况:
- 增长的寡核酸可溶性支结构的溶性对于高效的液相寡核酸合成 (LPOS) 是至关重要的.
- 溶解性差影响合效率,纯度和在寡核酸链延长期间的恢复.
- 优化可溶性支结构对于推动LPOS方法的发展至关重要.
研究的目的:
- 调查不同核基保护群对寡核酸可溶性支持结构的溶性的影响.
- 为了评估使用四脚式可溶性支架合成的受保护的寡核酸的回收和产量.
- 为了评估4-oxoheptanedioic acid (OHDA) 核酸释放链接器的正交.
主要方法:
- 在OHDA链接器衍生的四脚状可溶基上组装寡核酸.
- 使用5'-O-(2-甲基-2-yl) 保护的2'-脱氧核酸胺基构建块,具有多种核基保护组.
- 在不同的溶剂系统和抗溶剂中测量溶解度;使用RP HPLC和MS光谱评估产量和纯度.
主要成果:
- 调整核基保护组显著提高了在近极性有机溶剂中的构造溶解性.
- 在2-醇中的沉产生了接近量的中间体回收,产量从90%到量.
- 对合成的寡核酸 (高达五核酸) 和纯度的总产量进行了评估,证明了成功的LPOS.
结论:
- 核基保护组的战略选择是提高LPOS溶解度和恢复的关键.
- 来自OHDA链接器的四足体可溶性支物有助于高效合成具有良好的产量和纯度的寡核酸.
- OHDA链接器的直角性允许释放真正的受保护核酸.
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