Almost all cell surface proteins are modified by covalently-linked carbohydrates and the glycan structures on these glycoproteins are mediators of many physiological and disease processes. Despite their importance, there are no methods available to systematically and efficiently produce libraries of complex glycans to investigate specificities and biology of glycan binding proteins. To address this deficiency, we will develop synthetic methdologies that can provide large collections of glycans having architectures of unprecedented complexity. The methodology will be employed to prepare a series of keratan sulfate oligosaccharides. These glycoconjugates, which are biologically still poorly understood, have been implicated in a multitude of physiological and disease processes. To further broaden the scope of the technology, a chemoenzymatic methodology will be developed to prepare sialosides that at C-4, C-7, C-8 and/or C-9 are modified by acetyl esters. The compounds will be used to develop a designer glycan microarray to identify ligands for glycan binding proteins. The focus will be on immuno-regulatory proteins and viruses that exploit cell surface glycans for infectivity. Cellular arrays will be developed to examine biological properties of hits identified in the microarray screening. The results of the studies will provide critical insight about glycan complexity and recognition by self- and viral glycan binding proteins, and will provide leads for the development of immune-modulators and antiviral agents.
