Click and chemically triggered declick reactions through reversible amine and thiol coupling via a conjugate acceptor
Click and chemically triggered declick reactions through reversible amine and thiol coupling via a conjugate acceptor
复制标题
DOI：
10.1038/nchem.2601
复制
发表时间：
2016-10-01
期刊：
影响因子：
21.8
通讯作者：
Anslyn, Eric V.
中科院分区：
文献类型：
--
作者：
Diehl, Katharine L.;Kolesnichenko, Igor V.;Anslyn, Eric V.
分子单元的偶联和解偶是有机化学的一项基础性工作。在这里，我们报告了使用一种非常简单的从梅尔德鲁姆酸衍生的共轭受体，在中性pH条件下，在水条件下将胺和硫醇顺序地‘点击’在一起。随后，这种连接可以被化学触发器‘清除’，从而不受干扰地释放原始胺和硫醇。这种反应性不同于其他交联剂，因为顺序官能化的选择性来自于随着胺的加入而改变共轭受体的亲电性。我们描述了使用该程序来修饰蛋白质、创建多组份文库和合成低聚物，所有这些都可以在需要时以受控的方式被分解为它们的起始组分。由于反应条件温和，易于在各种应用中使用，因此该方法具有广阔的应用前景。
The coupling and decoupling of molecular units is a fundamental undertaking of organic chemistry. Herein we report the use of a very simple conjugate acceptor, derived from Meldrum's acid, for the sequential 'clicking' together of an amine and a thiol in aqueous conditions at neutral pH. Subsequently, this linkage can be 'declicked' by a chemical trigger to release the original amine and thiol undisturbed. The reactivity differs from that of other crosslinking agents because the selectivity for sequential functionalization derives from an altering of the electrophilicity of the conjugate acceptor on the addition of the amine. We describe the use of the procedure to modify proteins, create multicomponent libraries and synthesize oligomers, all of which can be declicked to their starting components in a controlled fashion when desired. Owing to the mild reaction conditions and ease of use in a variety of applications, the method is predicted to have wide utility.