金属有机骨架/氧化石墨烯复合材料的制备及其在磷酸化肽富集中的应用

Characterization of phosphorylation sites in proteins is an essential step to analyze the regulation of biological systems. Unfortunately, owing to the low abundance of phosphopeptides and the interference of non-phosphopeptides, it remains a great challenge for determination of phosphorylation sites using mass spectrometry (MS). The development of novel absorbent materials for selective enrichment of phosphopeptides from complex samples has become one of the research hotspots in phosphoproteomics presently. Metal-organic frameworks (MOFs) are the classes of microporous crystalline materials self-assembled from metal ions with organic linkers via coordination bonds. Their extraordinary physicochemical properties intensively stimulate their popularity in diversified applications. However, there are very few cases of the application of MOFs and their composites for selective enrichment of phosphopeptides. In this project, the studies on the preparation of MOF@graphene oxide (GO) composites as well as their application in the enrichment of phosphopeptides from biological samples are proposed. The open metal sites of MOFs could anchor the negatively charged phosphates of phosphopeptides through coordination bonds. GO herein acts as a structure-directing template in influencing the crystal growth of MOFs, which avoids the aggregation of nanomaterials and increases the solvent dispersibility. More importantly, the participation of GO could impart new crystal stucture and morphology to MOFs. This project would not only improve the preparation of MOFs based and graphene based composites but also extend their applications.

蛋白质中磷酸化位点的鉴定对于探索生物体系的调控机制至关重要。然而，磷酸化肽的低丰度、非磷酸化肽的干扰等因素的存在为质谱法鉴定磷酸化位点带来挑战。通过发展新型吸附材料实现从复杂样品中选择性富集磷酸化肽已成为目前磷酸化蛋白质组学的研究热点之一。金属有机骨架(MOFs)是一类由金属和有机配体自组装形成的多孔材料，因其独特的物理化学性质，在诸多领域表现出优越的应用前景。然而，MOFs及其复合材料在磷酸化肽富集中的应用研究鲜有报道。本项目拟研究MOF@氧化石墨烯(GO)复合材料的制备方法及其在选择性富集磷酸化肽中的应用。具有金属空位点的MOFs可以与磷酸化肽的磷酸根通过配位作用进行特异性结合。GO作为MOFs生长的结构导向模板，在避免MOFs颗粒团聚、增强溶剂分散性的同时，还有望使MOFs的晶体结构和形貌趋于多样化。本研究有助于MOFs和石墨烯基复合材料制备方法的完善以及应用领域的拓宽。

设计和制备了金属有机骨架材料和氧化石墨烯为基体的新型功能亲和吸附分离材料，研究了所制备的材料用于磷酸蛋白/多肽等生物大分子的选择性富集与分离，实现了项目设定的预期目标。此外还拓展了研究内容，设计和制备了多种稀土亲和材料、金属有机骨架材料和介孔功能材料，并对这些材料在生物样品前处理、蛋白质选择性分离富集、蛋白质药物传输等方面的应用做了大量研究。. 在石墨烯基多孔纳米吸附材料中，包括了聚多巴胺锚定钛离子的亲和吸附核壳材料、无模板冷冻干燥法制备的金属有机骨架材料(MIL-101)与石墨烯杂化而成的三维多孔结构的杂化气凝胶（MIL-101@GA）、适配体修饰的氧化石墨烯复合材料、氨基酸修饰的氧化石墨烯复合材料。以金属有机骨架材料MIL-100(Fe)为模型，在聚丙烯酸(PAA)改性的Fe3O4纳米颗粒表面层层自组装得到了核壳型MOF功能层。设计和制备了多种稀土亲和纳米材料，包括稀土氧化物功能化核壳结构 MnFe2O4@SiO2@ Lanthanide Oxides（La=Sm，Ce，Er，Tm，Yb）磁性材料、稀土(Er, Tm, Yb)硅酸盐功能化的磁性材料、植酸固定稀土Yb3+功能化的磁性材料等。