Glycocalyx engineering with tunable synthetic glycopolypeptides

All cells are coated with an array of glycoproteins, glycolipids, and polysaccharides that collectively form the glycocalyx. In bulk, the glycocalyx functions to hydrate, lubricate, and shield the cell from injury and infection. The glycocalyx also has biochemical functions and plays roles in essential process from adhesion and fertilization to infection and immunity. Glycoproteins are challenging to study at the molecular levels due to complex and heterogeneous glycosylation patterns that dynamically vary. These patterns are metabolically controlled and resist manipulation by traditional biochemical and genetic methods. Synthetic glycopolymers have emerged as useful tools to probe glycan based biological interactions. Glycosylated polypeptides are particularly attractive polymers since they can display glycans in their native form, take on natural secondary structures that are important for function, and are biodegradable. We have developed a chemical route to synthesize glycopolypeptides via polymerization of amino acid N ‐carboxyanhydrides. These glycopolypeptide are readily tunable in terms of molecular weight, composition, and glycan density and pattern. Our glycopolypeptides are also dual end‐functionalized with chemical handles that allow for conjugation to probes and biological targets. We have focused on preparing synthetic versions of cell‐surface human mucins and pathogenic glycopolypeptides associated with fungi and bacteria. Our results indicate that glycan pattern and protein‐linkage type have profound effects on conformation. We have also devised methods to engineer the glycocalyx by display these synthetic glycopolypeptides on the cell‐surface to probe and modulate biological outcomes. Overall, these are exciting new materials to systematically examine the role of glycosylation in protein conformation and bioactivity. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .