Sequence controlled glycopolymers for selective lectin targeting

碳水化合物结合蛋白（CBPs）介导多种生物功能，如内吞作用、宿主-病原体相互作用、细胞粘附和运输以及细胞内信号转导。一些糖蛋白的确切化学结构已经在文献中报道过。然而，即使是一小部分糖蛋白结构的化学合成也是极具挑战性的，并且与将它们整合到高度复杂的完整糖蛋白结构中相比，仍然可能没有表现出相同的生物活性。由于其多价性和结合各种CBPs的能力，糖共聚物（GP）已被证明具有模仿聚糖的功能，但它们缺乏CBP特异性。因此，开发具有精确序列控制、结构和折叠的系统GP文库，以确定它们与人类树突状细胞（DC）碳水化合物结合蛋白的特异性结合是非常有吸引力的。通过改变每条聚合物链的碳水化合物类型和数量、链上的微观结构分布和链的结构来增加编码的多样性，从而制备精确的GPs的高效化学途径将被研究。已知这些参数中的每一个都对特异性识别、结合动力学和直流信号传导有巨大的影响。人体内的糖密码是一个高度复杂和完善的机制，它负责各种生物识别事件。免疫系统相关细胞对碳水化合物结合蛋白的特异性识别对改善人类健康具有至关重要的意义。本项目关注于开发一系列含有大分子的合成碳水化合物，这些大分子可以靶向树突状细胞上的特定碳水化合物结合蛋白。这种合成糖密码的开发可能会为精确地将特定细胞靶向药物输送到选定的细胞打开大门。此外，这种糖结构会通过与某些凝集素的相互作用诱导细胞信号传导，从而激活细胞增殖或凋亡。

Carbohydrate binding proteins (CBPs) mediate diverse biological functions such as endocytosis, host-pathogen interactions, cell adhesion & trafficking and intracellular signal transduction. Exact chemical structures of some glycoproteins have already been reported in the literature. However, the chemical synthesis of even a small section of glycoprotein structures are extremely challenging and still may not exhibit the same biological activity in comparison to when they are incorporated into highly sophisticated complete glycoprotein structures. Glycopolymers (GP) have been shown to mimic glycan functions due to their multivalency and ability to bind various CBPs, but they lack CBP specificity. Thus development of systematic GP libraries with precise sequence control, architecture and folding in order to identify their specific binding to human dendritic cell (DC) carbohydrate binding proteins is highly appealing. Highly efficient chemical routes to prepare precision GPs while increasing the diversity in coding by altering carbohydrate type and number per polymer chain, microstructural distribution along the chain, and architecture of the chain will be investigated. Each of these parameters are known to have an enormous effect on specific recognition, binding kinetics and DC signalling. Sugar code in a human body is a highly complex and well established mechanism, which is responsible of various biological recognition events. The specific recognition of carbohydrate binding proteins on immune system related cells have a critical importance for improved health of humans. This project is concerned with developing a series of synthetic carbohydrate containing macromolecules that can target specific carbohydrate binding proteins on dendritic cells. The development of such a synthetic sugar code would potentially open the doors of precisely specific cell targeted drug delivery to selected cells. Moreover, such glyco structures would induce cell signalling upon interaction with certain lectins that may activate cell proliferation or apoptosis.