基于可裂解分子探针的糖蛋白/聚糖的质谱分析新方法研究

糖蛋白是生命活动中细胞信息功能的具体承担者，与很多疾病的发生、发展密切相关。建立针对糖蛋白肿瘤标志物的快速、灵敏、高通量的分析方法在疾病早期诊断及预后判断中显得尤为重要。本项目旨在结合可裂解分子探针策略和质谱技术，发展针对组织中糖蛋白质/聚糖的高灵敏和高通量质谱分析平台。创新性地将对聚糖的直接检测转化为对可裂解探针的检测，解决聚糖离子化效率低，谱图解析困难等问题。通过设计合成新型可裂解探针，结合质谱检测技术，建立对癌细胞/组织表面糖蛋白的质谱定量分析以及聚糖的原位、高灵敏质谱分析/成像方法，实现对疾病发生发展过程中蛋白质糖基化水平变化的直接监测，这对与肿瘤术中的快速辅助判断、发现新型肿瘤标志物和治疗靶标具有重要的意义。

Glycoproteins, as the bearer of the cellular signaling, involves in the development of a number of diseases. Aberrant level of protein glycosylation is closely related to cancer initiation and progression, thus glycoproteins are frequently used as clinical biomarkers. The establishment of the rapid, sensitive, high-throughput analytical method of glycoproteins is critical and on urgent demand in the disease diagnosis and prognosis. The aim of this project is combining the strategy of cleavable probe with Mass Spectrometry for the analysis of cell glycoproteins/glycans. This strategy innovatively converts the analysis of glycans to the detection of cleavable probes, overcoming the complicated composition and low ionization efficiency of glycans. Through the synthesis of novel cleavable probe and MS detection, quantitative analysis of glycoproteins/glycans on cell surface/tissue, and in situ, high sensitive MS analysis method can be established. The protein glycosylation level can be directly monitored along the development of diseases. It is absolutely significant and promising in the clinical judgement during surgery, observing novel cancer biomarker and therapeutic targets etc.