Sequence controlled glycopolymers for selective lectin targeting

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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.