项目名称：生物分离材料
项目来源：国家自然科学基金优秀青年科学基金
项目编号：21922411
项目金额：120万元（直接经费）
生物分离是生命科学研究的前提与基础，其核心是高性能分离材料的开发。围绕着提升分离材料的精确性与可控性，申请人构筑了一系列基于立体选择性氢键作用的生物分子精确识别体系，实现了石墨烯表面分子手性对阿兹海默症病理蛋白聚集过程的精确调控，及由溶剂诱导的凝胶-奎宁手性相互作用的反转。进而提出基于“手性识别-氢键调控-柔性主链”的生物分子响应性聚合设计思想，开发了手性单糖、核苷酸、短肽响应性薄膜及器件，将微弱的生物分子识别信号转换为材料表面宏观性质的大幅变化，由此发展一种全新手性色谱分离模式。随后将设计思想应用于磷酸化及糖基化蛋白质组学，提出新一代富集材料的典型特征。开发的智能聚合物实现了对多磷酸化肽高度可控的吸附与脱附及出色的富集选择性与吸附容量。基于二肽的聚合物将对糖肽的高选择性富集和对糖链结构的精确区分融为一体。本项目围绕甲基化肽富集材料的开发展开，尝试解决蛋白甲基化位点特异性识别和富集的挑战。
Title of funded project：Bio-separation Materials
Funding agency：National Natural Science Foundation of China, the National Science Fund for Excellent Young Scholars
Grant number：21922411
Total funding amount：CNY 1,200,000
Bio-separation is the prerequisite and foundation for research of life science, which strongly relies on the development of high performance separation materials. In order to substantially improve the precision, selectivity and controllability of bio-separation materials, a series of biomolecule–recognition systems driven by multiple stereoselective hydrogen bonding interactions were constructed. This facilitated precise manipulation of fibrillation process of Aβ-40 (an Alzheimer’s disease pathological peptide) on chiral amino acid–modified graphene oxide surface, as well as a solvent–modulated chiral interaction reversion for the complexation between a chiral gelator and (+)/(-)-quinine. Based on these biomolecule recognition receptors, a “chiral recognition–hydrogen bonding mediation–flexible main chain” based three–component polymer design idea was proposed to construct various chiral monosaccharide, nucleotide or oligopeptide–responsive copolymer thin films or bio-devices. Taking advantages of intelligent conformational transition of the polymeric chains triggered by synergetic hydrogen bonding interactions between the polymeric networks and the guest biomolecules, weak biomolecular recognition signals could be captured, recognized, transferred and amplified to remarkable variation in macroscopic properties of materials, such as surface wettability, stiffness, viscoelasticity or adhesion forces. Benefiting from these favorable changes in interfacial properties of materials, bio-separation efficiency might be improved significantly, contributing to a novel chiral chromatographic separation mode based on chiral interaction induced wettability switching. Subsequently, this biomolecule responsive polymer–design idea was successfully applied in phosphoproteomics and glycoproteomics. Highly controllable adsorption and desorption, satisfactory enrichment selectivity and high adsorption capacities toward multiple phosphopeptides were achieved on a smart polymer surface. Meanwhile, dipeptide–based homopolymers integrated high-efficiency glycopeptide enrichment and glycan precise discrimination into one system, which built a new bridge between proteomics and glycomics. Based on these studies, five typical characteristics of the new generation of phosphopeptide or glycopeptide enrichment materials were proposed. This project focuses on the development of methylated peptide enrichment materials, in order to tackle the challenge of protein methylated site-specific recognition and enrichment.