Complex Glycans in Health and Disease
Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602 (USA) and Utrecht University, Chemical Biology and Drug Discovery, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands
Most eukaryotic cell surface and secreted proteins are modified by covalently-linked glycans which are essential mediators of biological processes such as protein folding, cell signaling, fertilization, embryogenesis, and the proliferation of cells and their organization into specific tissues. Overwhelming data supports the relevance of glycosylation in pathogen recognition, inflammation, innate immune responses, the development of autoimmune diseases, and cancer. It has, however, been difficult to explore biological properties of individual glycans because these bio-molecules are not readily available. To address this challenge, we have developed chemo-enzymatic methodologies that make it possible to prepare libraries of highly complex asymmetrically substituted glycans including N- and O-glycans, human milk oligosaccharides (HMOs) and heparan sulfate oligosaccharides. The resulting compounds have been used to develop analytical protocols for exact structure determination of glycans, prepare glycoforms of glycoproteins and develop a micro-array platform for structure-binding studies. The glycan microarray has been used to examine the evolution of receptor specificities of respiratory viruses including Influenza A Virus, which will facilitate the implementation of surveillance strategies for viruses that pose pandemic threats.