糖基化聚膦腈的"点击化学"合成及其凝集素识别作用研究

Polymers containing saccharide groups have received increasing attention because of the rapid development of glycobiology. Clearly, issues around the successful combination of special biological functions of saccharide with the high designability of polyphosphazene, together with methods for constructing bionic functional glycosylated polyphosphazene, present considerable challenges at the leading edge of interdisciplinary science, involving polymer science, biomedicine and materials science. Potential future applications based on "yne-thiol" and "ene-thiol" click reactions will enable controllable and high-yield glycosylation and multi-configuration saccharide polyphosphazene to be put into practice. Moreover, polyphosphazene-based nano-saccharide aggregates and capsule may be prepared through self-assembly technique, with stable conformations and high glycosylation capacities. It is always preferable to establish the controlling method with reference to structure, morphology and properties. In the meantime, it is desirable to investigate the fundamental principles that will provide insights into how potential factors such as the constitution of glycosylated polyphosphazene, the structure (alpha-/beta-isomerism, epimerization, monosaccharide/oligo- saccharide) and capacity of the saccharide, the glycoside cluster effect and the nano-microstructure will affect the specific interactions between glycosylated polyphosphazene nano-aggregates, capsule surfaces and lectin protein molecules belonging to agglutinin. This work will provide theoretical insights and a technical basis for the utilization of glycosylated polyphosphazene to identify lectin proteins. Furthermore, it will expand the prospects for application of polyphosphazene in the biomedical field.

糖生物学的快速发展使得含糖聚合物受到了高分子科学的高度重视。如何将糖类化合物所特有的生物功能与聚膦腈侧基的高度可设计性进行有机结合，进而构建具有仿生功能的糖基化聚膦腈,是一项高分子化学与生物医学、材料科学等交叉渗透的前沿而富有挑战的课题。本课题提出基于炔基-巯基和烯基-巯基"点击化学"方法实现不同糖基密度、糖基构型聚膦腈的可控与高效合成，通过分子自组装技术制备出具有稳定形态结构和高糖基密度的聚膦腈基质纳米糖束和糖囊，建立其结构、形态与性能的调控方法，系统揭示糖基化聚膦腈化学组成、糖基结构(alpha-/beta-异构、差向异构、单糖/寡糖)、糖基密度、糖苷聚簇效应以及纳米微结构等因素对糖基化聚膦腈纳米糖束、糖囊与凝集素蛋白质分子相互作用的影响规律；为糖基化聚膦腈应用于凝集素蛋白质识别提供理论指导和技术基础，进一步拓展聚膦腈在生物医学领域的应用前景。

聚膦腈是一类以氮磷交替为主链的无机聚合物，具有良好的生物相容性、无毒降解性。如何将聚膦腈侧基的高度可设计性与糖所特有的生物功能进行有机结合，构建具有仿生功能的糖基化聚膦腈是一项高分子化学与生物医学、材料科学等交叉渗透的前沿而富有挑战的课题。由于传统的亲核取代修饰无法满足聚膦腈侧基结构的可控设计，本课题利用炔基-巯基和烯基-巯基“点击化学”方法实现糖基密度、不同糖基构型聚膦腈的可控与高效合成；通过分子自组装技术制备出具有稳定形态结构和高密度糖基化表面的聚膦腈基质纳米糖束和糖囊，建立其结构、形态与性能的调控方法；在此基础上，进一步研究了不同官能团聚膦腈对蛋白的亲和吸附能力，为糖基化聚膦腈应用于蛋白质识别提供理论指导和技术基础，进一步拓展聚膦腈在生物医学领域的应用前景。