在受到压力的细胞中，鉴定和捕获聚集蛋白的共价传感器非常罕见。在本文中，我们通过结构调控GFP色团并搭载环氧乙烷武器，构建了一系列共价荧光传感器用于聚集蛋白的检测。其中，P2探针选择性修饰了聚集蛋白而非折叠蛋白，并通过生化和质谱分析结果证明了荧光开启。我们证明了这种基于环氧乙烷的共价化学对不同类型的聚集蛋白具有广泛适应。最后，共价荧光传感器P2可直接可视化和捕获受压力的心肌细胞和来自心脏肿瘤鼠模型的心脏组织样品中的聚集蛋白。本文开发的环氧乙烷共价传感器可能成为未来鉴定心脏肿瘤发展机制的化学蛋白质组学分析的有用工具。Copyright © 2023 Elsevier B.V. All rights reserved.

Covalent sensors to detect and capture aggregated proteome in stressed cells are rare. Herein, we construct a series of covalent fluorogenic sensors for aggregated proteins by structurally modulating GFP chromophore and arming it with an epoxide warhead. Among them, P2 probe selectively modifies aggregated proteins over folded ones and turns on fluorescence as evidenced by biochemical and mass spectrometry results. The coverage of this epoxide-based covalent chemistry is demonstrated using different types of aggregated proteins. Finally, the covalent fluorescent sensor P2 allows for direct visualization and capture of aggregated proteome in stressed cardiomyocytes and cardiac tissue samples from a cardio-oncology mouse model. The epoxide-based covalent sensor developed herein may become useful for future chemical proteomics analysis of aggregated proteins to dissect the mechanism underlying cardio-oncology.Copyright © 2023 Elsevier B.V. All rights reserved.