Synthetic & Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry & Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, PR China.
College of Chemistry & Molecular Engineering, Peking University, Beijing 100871, PR China.
Future Med Chem. 2019 Dec;11(23):2979-2987. doi: 10.4155/fmc-2019-0221. Epub 2019 Oct 30.
Advanced glycation end products (AGE) are the biomarkers of aging and diabetes which are formed via reactions between glycating agents and biomacromolecules. However, no proteomic study has been reported to systematically investigate the protein substrates of AGEs. In this paper, we used an aniline-based probe to capture the glyoxal-imine intermediate which is the transition sate of glyoxal-derived AGEs. Combined with the tandem orthogonal proteolysis activity-based protein profiling strategy, we successfully identified 962 lysines modified by glyoxal. Enzymes in glycolysis are heavily modified by glyoxal and our biochemical experiments showed that glyoxal can significantly inhibit the activity of GAPDH and glycolysis. These data indicated that AGEs modifications may contribute to pathological processes through impairing the glycolytic process.
晚期糖基化终末产物 (AGE) 是衰老和糖尿病的生物标志物，它是通过糖基化试剂与生物大分子之间的反应形成的。然而，目前还没有蛋白质组学研究系统地研究 AGEs 的蛋白质底物。在本文中，我们使用一种基于苯胺的探针来捕获糖醛-亚胺中间体，这是糖醛衍生的 AGEs 的过渡状态。结合串联正交蛋白水解活性的基于蛋白的蛋白谱分析策略，我们成功地鉴定了 962 个被糖醛修饰的赖氨酸。糖酵解中的酶被糖醛严重修饰，我们的生化实验表明，糖醛可以显著抑制 GAPDH 和糖酵解的活性。这些数据表明，AGEs 的修饰可能通过损害糖酵解过程来导致病理过程。
