近日，我组（生物分离与界面分子机制创新特区研究组，18T7）和分离材料化学与组分中药研究组（1803组）梁鑫淼研究员团队合作，提出了一种全新的基于席夫碱水解的动态共价化学方法，实现了对唾液酸糖链的精确捕获。
唾液酸糖链在细胞膜表面具有丰富的分布，如同一层“糖被”覆盖在细胞表面。这种最外端位置及其广泛的分布，使得唾液酸糖链在病毒感染、免疫激活、癌症发生、发展和迁移等诸多生理过程中，发挥着至关重要作用。因此，唾液酸糖蛋白已被广泛用作癌症的临床生物标志物。然而，唾液酸糖链的鉴定及分析异常复杂，迫切需要全新、高效的材料学体系，以攻克复杂生物样本中唾液酸糖肽富集和分离的瓶颈，推动糖蛋白组学的全面发展。
我组首次报道基于动态共价化学的策略，用于唾液酸糖链的精确捕获。该策略与传统的静态亲合策略截然不同，巧妙地利用了席夫碱中存在的动态共价化学键，以及其水解部分与唾液酸糖链形成稳定的复合物，所开发的材料对唾液酸糖肽展现出非常优异的富集选择性，高的吸附容量和富集回收率，达到了唾液酸糖肽富集领域的最高水平。这为生物化学家提供了一种新颖、强大和具有里程碑意义的策略，可用于精确地捕捉与癌症和免疫疾病发生密切相关的糖链信息。另一方面，该席夫碱材料易于水解的特性，完全颠覆了传统富集材料必须具备良好化学稳定性的认知。更重要的是，研究人员发现希夫碱水解反应背后隐藏着一个激动人心的故事，展现了动态共价化学在糖蛋白组学和生物分子传感领域的独特优势。
相关成果发表在《美国化学会志》（J. Am. Chem. Soc. 2020, DOI: 10.1021/jacs.0c01970, https://pubs.acs.org/doi/10.1021/jacs.0c01970）上，第一作者是18T7组博士后熊雨婷和1803组李秀玲研究员。以上研究工作得到国家自然科学基金项目、我所创新特区组启动基金、兴辽英才计划等项目的支持。同时周永贵研究员，石松研究员对工作进行了有益的指导，生物技术部、能源测试仪器平台、化物所各职能部门给予了大力的培育和支持！
What is hidden behind Schiff base hydrolysis? Dynamic covalent chemistry for precise capture of sialylated glycans
Yuting Xiong, Xiuling Li, Minmin Li, Haijuan Qin, Cheng Chen, Dongdong Wang, Xue Wang, Xintong Zheng, Yunhai Liu, Xinmiao Liang,* Guangyan Qing*
J. Am. Chem. Soc. 2020.
DOI: 10.1021/jacs.0c01970
The aberrant expression of sialylated glycans (SGs) is closely associated with the occurrence, progression, and metastasis of various cancers, and sialylated glycoproteins have been widely used as clinical biomarkers for cancers. However, identification and comprehensive analysis of SGs is exceptionally complex, which urgently need innovative and effective method to capture SGs from biosample in prior to MS analysis. Here, we report that a novel dynamic covalent chemistry strategy based on Schiff base hydrolysis can be applied for the precise capture of the SGs. The prepared Glucopyranoside-Schiff base-modified silica gel displays extraordinary enrichment selectivity (even at the ratio of 1:5000 with interference), high adsorption capacity (120 mg·g−1), and satisfying enrichment recovery (95.5 %) towards sialylated glycopeptides, which contributes to a highly specific, efficient, mild and reversible SG capturing approach that can remarkably promote the development of glycoproteomics and sialic acid sensing devices, and can be considerably promising in cancer biomarker discovery. Meanwhile, the facile hydrolysis characteristic of our Schiff base material completely subverts conventional knowledge of enrichment materials, the chemical stability of which is usually regarded as a prerequisite. Importantly, we find an exciting story hidden behind the Schiff base hydrolysis reaction, which demonstrates the unique advantage of dynamic covalent chemistry in glycoproteomics and biomolecule sensing.
