蛋白磷酸酶活性的光电化学-压电双模式免标记分析

蛋白质磷酸化和去磷酸化是调节和控制蛋白质活力和功能的最基本、最普遍、也是最重要的机制。蛋白磷酸酶缺乏或调节失常与多种疾病有关，包括癌症、糖尿病、肥胖症、老年痴呆症等。本项目拟发展形貌、大小可控的多孔二氧化锆纳米多面体基高性能光电活性材料，基于磷酸根与锆间强螯合作用、及光电化学和压电传感技术的优势，构建新型光电化学-压电双模传感平台，实现单一蛋白磷酸酶/复合蛋白磷酸酶活性的免标记高灵敏检测和蛋白磷酸酶催化磷酸化蛋白质/磷酸化多肽去磷酸化过程的实时监测，开展蛋白磷酸酶抑制剂的快速筛选研究。通过本项目研究，将促进对蛋白质去磷酸化相关的生命活动的认知，有助于由蛋白磷酸酶异常引发的各种疾病的诊断，促进以蛋白磷酸酶为靶点的相关药物研发。首次提出的光电化学-压电双模传感平台为目标物定量检测和相关动力学过程实时监测等提供了新的分析方法，在生物分析、疾病诊断和药物开发等方面具有潜在应用前景。

Protein phosphorylation and dephosphorylation are the most basic, most general and most important mechanisms that regulate and control the activity and function of proteins.. The deficiency or regulation disorder of protein phosphatase are related to many diseases, including cancer, diabetes, obesity, Alzheimer's disease, etc. This project plans to develop porous ZrO2 nanopolyhedron-based high-performance photoelectric active materials with controllable morphology and size. Based on the strong chelation between phosphate and Zr, and the advantages of photoelectrochemical and piezoelectric sensing technologies, the new photoelectrochemical-piezoelectric dual-mode sensing platforms are constructed, the label-free and ultra-sensitive assays for the activities of the single protein phosphatase and the mixed protein phosphatases are performed, the dephosphorylation kinetics of the phosphorylated proteins and peptides catalyzed by protein phosphatases are monitored in real time, and the rapid screening of protein phosphatase inhibitors is carried out. This project will promote the understanding of life activities related to protein dephosphorylation, be helpful for the diagnosis of various diseases caused by the abnormality of protein phosphatase, and promote the development of the related drugs targeting protein phosphatase. The photoelectrochemical-piezoelectric dual-mode sensing platform, which is proposed for the first time, provides a new analytical method for quantitative detection of target and real-time monitoring of the related dynamic process, and has potential applications in biological analysis, disease diagnosis and drug development.