基于模板辅助-定向表面印迹策略的分子印迹金属有机框架化合物的制备及其在糖蛋白组学中的应用

The specific affinity between antigen and antibody plays important role in modern analytical approaches for scientific researches. Molecular imprinting is an important technology to produce biomimetic materials with antibody-like specificity. Imprinting approaches can be classified into three major strategies: bulk imprinting, bead-forming imprinting and surface imprinting. Although there have been much efforts to improve the performances of these imprinting technologies, they still suffer from several drawbacks. Especially, the properties of imprinted materials are highly dependent on the substrate materials. Thus, the combination of molecular imprinting and advanced material, such as porous material, will greatly promote the development of high-performance biomimetic materials. Metal-organic frameworks (MOFs) are newly emerged hybrid inorganic-organic microporous crystalline materials self-assembled straightforwardly from metal ions with organic linkers via coordination bonds. The availability of various building blocks of metal ions and organic linkers makes it possible to prepare an infinite number of new MOFs with diverse structures, topologies, and porosity, which make MOFs attractive for analytical applications. Up to date, a general approach for preparing molecularly imprinted MOFs has not been established yet. This project aims at developing a general and high efficient approach for molecularly imprinted MOFs by the virtue of template assisted-oriented surface imprinting. With the introduction of mesopores’ template (CTAB micelle) into the synthetic procedure of MOFs, the high efficient imprinting process could be achieved without additional experimental steps. Furthermore，a glycopeptide-imprinted MOFs will be prepared via the proposed imprinting strategy, multiple analytical approaches (affinity separation, SALDI-MS) will be developed for the proteomics analysis. This project can not only promote the development of molecular imprinting technology, but also expand the applications of the advanced biomimetic materials in proteomics analysis.

基于抗原-抗体间特异性识别作用的分析方法在现代科学研究中应用广泛。分子印迹是制备具有类似抗体识别性能材料的重要策略。目前，虽然分子印迹技术已有了长足发展，但尚缺少适用于多孔材料的高效印迹策略。金属有机框架化合物作为近年来出现的一类先进多孔材料，其独特的理化性质可以极大的拓展现有分子印迹材料的应用范围。然而文献中尚未有关于分子印迹金属有机框架化合物的报道。有鉴于此，本项目拟将致孔模板引入到金属有机框架化合物的制备体系中，借助致孔模板-印迹模板及印迹模板-印迹单体之间的相互作用，发展出用于制备分子印迹金属有机框架化合物的模板辅助-定向表面印迹策略。同时，本项目还将以糖肽为模板，探索印迹材料的在糖蛋白组学中的应用，发展出多种适用于组学分析的新型分析方法。本项目的研究不仅能促进分子印迹技术的发展，还能进一步拓展仿生亲和材料在蛋白质组学中的实际应用。

本项目针对蛋白质组学分析中的关键科学问题-目标分子的选择性富集与检测，围绕着具有特异性识别能力亲和材料的设计与合成，结合金属有机框架化合物独特的理化性质，开展了系列研究。完成了具有特异性识别能力的金属有机框架化合物的制备，并针对印迹模板分子对其合成策略进行了优化。在此基础上，结合表面辅助激光解析电离-飞行时间质谱技术，实现了多种功能分子的原位富集与质谱检测。合成了具有特异性识别能力的金属有机框架化合物，实现了肾上腺素，儿茶酚，脂肪酸，稠环芳烃等分子的富集与质谱检测。同时，我们还针对大分子蛋白质这种印迹模板分子，对项目进行中需采用的定向表面印迹策略进行优化。此外，我们还以此为基础，建立了中药有效成分的高效分析策略，与标准方法相比，在保证结果准确性的基础上，极大的优化了实验步骤。本项目目前已发表SCI论文4篇，另有1篇论文在整理中。