Use of activity-based probes to study the action of glycosidases

使用基于活性的探针研究糖苷酶的作用

• 批准号: 1941670
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1941670
• 关键词: Use; activity; based; probes; study

The development of new approaches to dissect the diverse and wonderful roles for carbohydrates in living cells is a major challenge for modern cell biology, biochemistry and medicine. The colossal potential of carbohydrates is reflected in the multiplicity of functions for glycans; in addition to acting as energy sources, carbohydrates play central roles in cell and organism structure, communication signalling and epigenetic modification. This project will build upon recent developments in the activity-based profiling of carbohydrate-degrading enzymes termed gycosidases; notably in the context of lysosomal storage diseases. The student will initially analyse binding of "next-generation" probes to the human Gaucher and Fabry disease enzymes. 3-D structure will inform the synthesis of improved probes. Probes will be used to quantity enzyme activity in healthy and disease cells, working in collaboration with Overkleeft and Aerts, Leiden possibly leading to the development of new diagnostic technologies. As the project evolves, we expect to see the probe concept rolled-out to other enzyme classes and applications and ultimately, we would like to combine such techniques with cryo-electron tomography approaches to probe the activity of enzymes within living cells.

发展新的方法来剖析碳水化合物在活细胞中的各种奇妙作用是现代细胞生物学、生物化学和医学面临的主要挑战。碳水化合物的巨大潜力反映在聚糖功能的多样性上；除了作为能量来源，碳水化合物在细胞和生物体结构、通讯信号和表观遗传修饰中起着核心作用。该项目将建立在被称为糖苷酶的碳水化合物降解酶的活性分析的最新发展基础上；特别是在溶酶体贮积病的背景下。学生将首先分析“下一代”探针与人类戈谢病和法布里病酶的结合。三维结构将为改进探针的合成提供信息。探针将用于测量健康细胞和疾病细胞中的酶活性，与Overkleeft和Aerts， Leiden合作，可能会导致新的诊断技术的发展。随着项目的发展，我们希望看到探针概念推广到其他酶类和应用中，最终，我们希望将这种技术与低温电子断层扫描方法结合起来，探测活细胞内酶的活性。