蛋白糖基化是生命科学研究的前沿方向，与肿瘤癌症发生，免疫应答，细胞通讯等密切相关。新型糖肽富集材料的开发很好地解决了唾液酸型糖肽富集的难题，然而对于O-连接糖肽、中性糖肽的特异性富集，仍是一个巨大的挑战。迫切需要引入新的材料学体系，提升富集的精确性和捕获效率。本项目以共价有机骨架材料（COFs）为载体，在COFs上引入氨基酸、寡肽、寡糖等功能识别单元，构造全新的有机功能富集材料。COFs具有化学稳定性好、结构裁剪性强、孔结构精细可调等优点，同时借助功能识别单元的多重氢键位点，以及孔内多单元协同的相互作用，实现对糖肽的选择性识别与高亲和力结合。进而构建材料对糖肽富集方法学，借助细胞裂解液、血清等实际样品进行验证。探索材料对肠癌组织样本中糖肽的捕获能力，构建糖基化表达异常与疾病之间的关系。COFs基新介质的引入，有望为糖肽的特异性富集和分离提供一种新方法、新思路。

As one of the most common post-translational modification (PTM) types, reversible protein glycosylation plays crucial regulatory roles in almost all aspects of cellular processes, which is vital to tumor cancer, immune response and cell communication. At present, a group of novel glycopeptide enrichment materials were emerged to effectively solve the selective enrichment of sialylated glycopeptides. However, the remaining problems such as the specific enrichment of O-linked glycopeptides or neutral glycopeptides are still the core of the field. Thus, developing new generation of separation materials is quite urgent for promoting the enrichment accuracy and capture efficiency. In this project, covalent organic frameworks (COFs) provide continuous and confined open channels at the nanoscale, affording an accessible high surface area interface for modification. Functional units including amino acids, oligopeptides, and oligosaccharides are introduced to graft onto the surface of COFs hollow sphere, in order to the design of new organic functional enrichment materials. COFs has the advantage of chemical stability, customizable surface characteristics, and pore environment control. The ability to easily tune the construction unit of a COF using monomers bearing specific functional groups can improve its selective recongnition and highly compatibility with glycopeptides, in combination with the multiple hydrogen bonding sites, and the multi-cell collaborative interaction in the pore channels. Meanwhile, the selective enrichment method for glycopeptides will be established and validated with cell lysis buffer and serum samples. Based on these, we will do some exploratory research in areas like abnormal expression in intestinal cancer, and try to establish the relationship between glycosylation and disease. We believe this project will have important scientific significance and potential application value in the field of glycoproteomics, and provide an original strategy for the glycopeptide enrichment.