侧链结构有序的树枝化含糖聚合物的合成及其对凝集素特异识别作用研究

The specific recognition of highly-ordered glycopolymers containing different carbohydrate units with lectins plays an important way to expand the biological application of glycopolymers. However, highly-ordered glycopolymers containing different carbohydrate units have scarcely been studied due to the lack of efficient methods to prepare this type of glycopolymers. The mechanism of synergistic effects of different sugar motifs to recognition events between glycopolymers and lectins is not quite clear and will need further systematical investigation. Side-chain ordered dendronized glycopolymers will be achieved by combining ring-opening metathesis polymerization (ROMP) and thiol-ene reaction in this project based on our previous work. Highly-ordered dendronized macro-glycomonomers will be prepared by using thiol-ene reaction, while the ratio of different glycol-units is controllable. Subsequently, the macro-glycomonomers will be polymerized via living ring-opening metathesis polymerization (ROMP) to give novel well-defined functional glycopolymers with the highly-ordered side chain, while employing the lengths and structures of the linker to decrease the steric effects. By changing the ratios of different carbohydrate units in side chain, the potential synergistic effects to recognition events between glycopolymers and lectins will be systematically studied taking α-mannose-lectin Concanavalin (Con A) as a model. The results would provide experimental and theoretical basis for improving the ability of specific recognition of glycopolymers and the design of functional glycopolymers for biological applications.

含不同糖单元的结构有序糖类聚合物与凝集素的特异性识别作用是拓展含糖聚合物在生物应用方面的重要途径之一。而结构有序的含不同糖单元的聚合物制备相对较少，缺少高效的聚合物合成方法；不同糖单元在含糖聚合物对凝集素特异识别作用过程中所呈现的协同效应机理尚不明晰，缺乏系统性实验研究。本项目拟在原有工作基础上，联姻巯基-烯烃加成反应和活性开环移位聚合（ROMP）制备侧链结构有序的树枝化含糖聚合物。利用巯基-烯烃加成，制备有序结构的含不同糖单元的树枝化大分子单体（不同糖单元比例可控）；利用活性ROMP聚合，通过改变单体中链接基团的长度和类型减少位阻效应，制备侧链高度有序、结构规整的功能性树枝化聚合物；以α-甘露糖-凝集素刀豆蛋白（Con A）为模型，通过改变侧链中不同糖单元的比例，系统考察其潜在的协同效应，为提高含糖聚合物对凝集素的特异识别能力及设计具有特殊生物功能的含糖聚合物提供实验和理论依据。

本项目完成预期目标，通过联姻巯基-烯烃加成反应或CuAAC反应和 ROMP聚合反应，制备侧链结构高度有序的异类含糖聚合物；并进一步采用“后改性”策略，发展了结合CuAAC反应和RAFT聚合制备侧链有序结构异类含糖聚合物的方法；以含α-甘露糖含糖聚合物对Con A 特异识别作用为模型，研究异类含糖聚合物与凝集素的特异识别作用以及不同糖单元的协同效应。结果表明β-葡萄糖和β-半乳糖的存在促进了α-甘露糖与Con A的结合，进一步协同效应存在于含糖聚合物与Con A的识别过程，为提高含糖聚合物的特异识别能力，拓展含糖聚合物在生物领域的应用前景提供了实验和理论依据。总之，在本项目资助下，项目负责人顺利完成了既定研究目标，在含糖聚合物的合成方面取得了一些新进展，以通讯作者发表了3篇研究论文，申请8项国家发明专利。