项目名称：酪氨酸磷酸化肽智能捕获材料
项目来源：国家自然科学基金面上项目
项目编号：22174138
项目金额：60万元
酪氨酸磷酸化及其激酶参与调控了多个重要的生物学过程，包括细胞增殖、周期进程、迁移、凋亡、血管生成、基因转录和代谢反应等。它是细胞信号转导中的关键因子，在肿瘤的发生发展中发挥着关键性作用。截止2019年美国FDA已批准52种小分子激酶抑制剂，其中63%是酪氨酸激酶抑制剂。通过质谱对蛋白酪氨酸磷酸化的规模化鉴定，可以获取其对应的激酶活性和相关信号通路的信息，对于抗肿瘤药物的研发与临床应用均具有十分重要的意义。然而酪氨酸磷酸化蛋白质组学的质谱分析受到重重挑战，迫切需要开发对酪氨酸磷酸化肽具有特异性识别能力的捕获材料与技术。本项目提出通过学习SH2超亲体核心的结合位点，构筑一系列基于胍类分子的智能聚合物，并将其开发为色谱富集材料，用于酪氨酸磷酸化肽的高效富集分离。新材料的融入和方法学的开发将有助于动态、整体地测定疾病发生过程中蛋白激酶种类、数量和结构的变化，发现疾病诊断、预后标志物和药物治疗靶点。
Title of funded project：Smart enrichment materials for tyrosine phosphorylated peptides
Funding agency：National Natural Science Foundation of China
Grant number：22174138
Total funding amount：CNY 600,000
Tyrosine phosphorylation and its kinases participate in the regulation of many important biological processes, including cell proliferation, cycle progression, migration, apoptosis, angiogenesis, gene transcription, and metabolic reactions. In particular, they are key factors in cell signal transduction and play key roles in the occurrence and development of tumors. As of 2019, the US FDA has approved 52 small molecule protein kinase inhibitors, of which 63% are tyrosine kinase inhibitors. The large-scale identification of protein tyrosine phosphorylation by mass spectrometry can obtain information about its corresponding kinase activity and related signal pathways, which is of great significance for the development and clinical application of antitumor drugs. However, the mass spectrometry analysis of tyrosine phosphorylated proteomics encounter many challenges, and there is an urgent need to develop advanced enrichment materials and technologies that can specifically recognize tyrosine phosphorylated peptides. This project proposes to build a series of smart polymers based on guanidine molecules by learning the binding sites of the SH2 superbinder core, and develop them as chromatographic enrichment materials for efficient enrichment and separation of tyrosine phosphorylated peptides. The integration of new materials and the development of methodology will help to dynamically and holistically identify the changes in the types, quantities and structures of proteins kinases in the course of disease occurrence, discovering disease diagnosis, prognostic markers and drug treatment targets.
