Sequence controlled glycopolymers for selective lectin targeting

碳水化合物结合蛋白（CBPs）介导多种生物学功能，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。一些糖蛋白的精确化学结构已经在文献中报道。然而，即使是糖蛋白结构的一小部分的化学合成也是极其具有挑战性的，并且与当它们被并入高度复杂的完整糖蛋白结构时相比，仍然可能不表现出相同的生物活性。由于其多价性和结合各种CBP的能力，已显示糖共聚物（GP）模拟聚糖功能，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文库以鉴定其与人树突细胞（DC）碳水化合物结合蛋白的特异性结合是非常有吸引力的。高效的化学路线，以制备精确的GP，同时增加编码的多样性，通过改变碳水化合物的类型和数量每个聚合物链，微观结构分布沿着链，和结构的链将被调查。已知这些参数中的每一个对特异性识别、结合动力学和DC信号传导具有巨大影响。人体中的糖密码是一种高度复杂且已建立的机制，它负责各种生物识别事件。免疫系统相关细胞上的碳水化合物结合蛋白的特异性识别对于改善人类的健康具有至关重要的意义。本研究旨在开发一系列合成的含碳水化合物的大分子，这些大分子可以靶向树突状细胞上的特异性碳水化合物结合蛋白。这种合成糖密码的开发将有可能打开精确的特定细胞靶向药物递送到选定细胞的大门。此外，这种糖结构在与某些凝集素相互作用时会诱导细胞信号传导，这可能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.