Abstract：
High temperature requirement A serine proteases (HTRA) are ubiquitously expressed and participate in protein quality control and cellular stress responses. They are linked to several clinical illnesses, including bacterial infection, cancer, age-related macular degeneration, and neurodegenerative diseases. In addition, several recent studies have revealed HTRAs as important biomarkers and potential therapeutic targets, necessitating the development of an effective detection method to evaluate their functional states in various disease models. We developed a new series of HTRA-targeting activity-based probes with enhanced subtype selectivity and reactivity. In conjunction with our previously developed tetrapeptide probes, we established the structure-activity relationship of the new probes for different HTRA subtypes. Our probes are cell-permeable and have potent inhibitory effects against HTRA1 and HTRA2, making them valuable for identifying and validating HTRAs as an important biomarker.
摘要：
高温要求丝氨酸蛋白酶(HTRA)普遍表达并参与蛋白质质量控制和细胞应激反应。它们与几种临床疾病有关，包括细菌感染,癌症,年龄相关性黄斑变性,和神经退行性疾病。此外,最近的几项研究表明，HTRAs是重要的生物标志物和潜在的治疗靶标，需要开发一种有效的检测方法来评估其在各种疾病模型中的功能状态。我们开发了一系列新的基于HTRA靶向活性的探针，具有增强的亚型选择性和反应性。结合我们以前开发的四肽探针，我们建立了不同HTRA亚型新探针的构效关系。我们的探针具有细胞渗透性，并且对HTRA1和HTRA2具有有效的抑制作用，使它们对于识别和验证HTRAs作为重要的生物标志物很有价值。
