利用高通量SPR微阵列芯片对类肽-蛋白亲和作用的研究

There is severe scarcity of high quality antibodies which can be used for protein separation, enrichment and measurement. With their property of low MW, low cost, protein affinity reagents made by chemical synthesis are of great value for quantitative proteomics. Peptoid is a non-native oligomer composed of N-(substituted)glycines. Having the advantage of high variety of conformation, high stability of structure and high efficiency for synthesis, peptoids might be used as a new class of protein affinity reagents. A new type of peptoid microarray platform will be constructed based on Surface Plasmon Resonance Imaging (SPRi) for high-throughput screening and analysis of peptoid libraries. The project will focus on the study of the strategy of "synthetic capture", which means to link the two noncompetitive peptoid monomers into a bivalent dimer through a linker to improve the affinity and specificity. Through the systematical study of the molecular mechanism of the interaction between peptoids and proteins and the comprehensive optimization of the technical route, the project will explore the application of peptoids as the protein affinity reagents from the point of view of theory and technology.

目前，能够用于蛋白的分离、富集和检测的优质抗体种类远远不够。化学合成亲和试剂具有分子量小，成本低廉的特点，对定量蛋白质组学具有重要意义。类肽是由N-取代甘氨酸组成的非天然聚合物，具有构象多样，结构稳定，合成效率高的优点，有可能成为新型的蛋白亲和试剂。本研究拟建立基于表面等离子体共振成像技术（SPRi）的类肽微阵列芯片分析平台，用于类肽文库的高通量筛选和亲和作用的分析。重点在于"协同捕获"策略的研究，通过连接骨架将非竞争结合的两个单体类肽连接形成二元类肽，提高其亲和力和特异性。通过系统地研究类肽-蛋白质亲和作用的分子机制，全面优化技术路线，为类肽作为蛋白亲和试剂的应用进行理论和技术探索。

目前，能够用于蛋白的分离、富集和检测的优质抗体种类远远不够。化学合成亲和试剂具有分子量小，成本低廉的特点，对定量蛋白质组学具有重要意义。类肽是由N-取代甘氨酸组成的非天然聚合物，具有构象多样，结构稳定，合成效率高的优点，有可能成为新型的蛋白亲和试剂。本研究拟建立基于表面等离子体共振成像技术（SPRi）的类肽微阵列芯片分析平台，用于类肽文库的高通量筛选和亲和作用的分析。重点在于“协同捕获”策略的研究，通过连接骨架将非竞争结合的两个单体类肽连接形成二元类肽，提高其亲和力和特异性，为类肽作为蛋白亲和试剂的应用进行理论和技术探索。在本项目的支持下，共发表SCI论文23篇，申请发明专利13项，另有学术专著一部。