持久性有毒污染物（PTS）是备受关注的全球性环境问题。已有研究表明PTS会对人类的生存和健康带来危害。蛋白质糖基化是一种重要的蛋白质功能调节机制，其中负责催化糖基化的糖基（或去糖基）转移酶的活性会受到小分子化合物的调控。由于PTS毒性作用机制的复杂性，PTS是否会干扰蛋白质糖基化过程及可能的干扰机制，鲜有报道。其中一个重要原因是缺乏蛋白质糖基化的有效研究手段。本项目拟建立一种简单、快速、免标记的电化学传感检测方法。在氧化铟锡电极表面共价固定酶底物-含酪氨酸的多肽分子，以酪氨酸为信号分子，利用多肽糖基化前后蛋白酶对其水解能力的差异，导致酪氨酸电催化信号的改变，实现对蛋白质可逆糖基化的检测，在此基础上，进行PTS对蛋白质可逆糖基化过程干扰效应的快速筛查，建立定量结构-活性关系模型，深入探讨污染物毒性分子作用机制及可能致病机理。该项目将为PTS对生物标志物酶的毒性作用的筛查和研究提供一种新方法。

Persistent toxic substances (PTS) is increasingly concerned as a global environmental problem. Some research shows that PTS is harmful to human health. Protein glycosylation plays an important role in function regulation of protein. It occurs through the action of glycosyltransferase and deglycosyltransferase. Meanwhile, the activities of these two enzymes can be precisely regulated by small-molecule compounds. Due to the complexity of PTS toxicity mechanism, whether PTS can interfere with the reversible protein glycosylation or not and the possible interference mechanism is unclear. The most important reason is due to the lack of effective analytical method for protein glycosylation. A simple, fast and label-free electrochemical sensing method for the detection of reversible protein glycosylation will be developed. Tyrosine-containing polypeptide, as a substrate of enzyme, is covalently immobilized on the surface of indium tin oxide electrode. The tyrosine residue in the polypeptide serves as an electrochemical signal reporter. Its voltammetric current is catalyzed by a dissolved electron mediator. The proposed protocol for monitoring the reversible polypeptide glycosylation is feasible based on the difference of electrochemical signal between glycosylated and non-glycosylated polypeptide due to the distinct electro-catalyzed tyrosine oxidation, which results from the change of degradation amount in glycosylated and non-glycosylated polypeptide. On this basis, the interference effects of PTS on the reversible protein glycosylation will be screened. The quantitative structure-activity relationship of PTS will be established. The PTS toxicity and pathogenetic mechanism will be explored in detail. This promising strategy can be implemented as a new method for screening and studying the PTS toxic effects on the biomarker enzymes.