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化学选择性循环和直接在未受保护的上循环
Yue Zhang1, Qing Zhang1, Clarence T T Wong2
1Department of Chemistry, State Key Laboratory of Synthetic Chemistry , The University of Hong Kong , Hong Kong , P. R. China , SAR.
Journal of the American Chemical Society
|July 18, 2019
概括
一种新方法使用正方体甲 (OPA) 直接循环化无保护,形成异能桥循环. 这种简单的基于水的方法可以为循环库的开发提供多种修饰和生物结合.
科学领域:
- 化学生物学
- 有机化学
- 类化学
背景情况:
- 循环是生物分子相互作用的关键调节剂.
- 对于和非化学家来说,构建循环库的有效方法是必要的.
- 目前的循环化方法通常需要保护/解除保护的步骤,这限制了它们的简单性和范围.
研究的目的:
- 开发一种高化学选择性且操作简单的方法,用于未受保护的的直接循环.
- 探索正甲 (OPA) 在形成新型循环结构中的实用性.
- 扩大循环后修饰和生物结合的能力.
主要方法:
- 使用正甲 (OPA) 的未受保护的直接循环.
- OPA与水性缓冲体中的 lysine/N-terminus 和 cysteine 残留物发生反应
- 用于双循环合成的原生化学结合.
- 使用N-maleimide部分的OPA循环的单功能化.
主要成果:
- 从未受保护的序列中成功形成异能桥循环.
- 在水性缓冲剂中证明了化学选择性,功能组耐受性和操作简单性.
- 通过将OPA循环与原生化学结合来实现双环的简单合成.
- 能够将多种功能性基因 (,甘氨酸,,DNA) 一次引入到循环上.
结论:
- 通过OPA介导的循环化为产生多种循环提供了一种简单而多用途的策略.
- 这种方法简化了循环库的构建,并促进了先进的生物结合.
- OPA循环化方法显著扩大了化学家和生物结合应用的合成工具箱.
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