Abstract：
Quenched activity-based probes (qABP) are invaluable tools to visualize aberrant protease activity. Unfortunately, most studies so far have only focused on cysteine proteases, and only a few studies describe the synthesis and use of serine protease qABPs. We recently used phosphinate ester electrophiles as a novel type of reactive group to construct ABPs for serine proteases. Here, we report on the construction of qABPs based on the phosphinate warhead, exemplified by probes for the neutrophil serine proteases. The most successful probes show sub-stoichiometric reaction with human neutrophil elastase, efficient fluorescence quenching, and rapid unquenching of fluorescence upon reaction with target proteases.
摘要：
基于活性的猝灭探针（qABP）是可视化异常蛋白酶活性的宝贵工具。不幸的是,到目前为止，大多数研究只集中在半胱氨酸蛋白酶上，只有少数研究描述了丝氨酸蛋白酶qABP的合成和使用。我们最近使用次膦酸酯亲电体作为一种新型的反应基团来构建丝氨酸蛋白酶的ABP。这里,我们报告了基于次膦酸盐弹头的qABP的构建，以嗜中性粒细胞丝氨酸蛋白酶的探针为例。最成功的探针显示与人中性粒细胞弹性蛋白酶的亚化学计量反应，高效的荧光猝灭，与靶蛋白酶反应后荧光快速解猝灭。
