Sulfated oligosaccharides and selectin ligands.

摘要

This study was undertaken to identify and characterize sulfated oligosaccharides which are unique in structure and/or are responsible for specific biological functions. The choice to look specifically at sulfated oligosaccharides, is based on the hypothesis that oligosaccharide modifications such as sulfation, are a potential way in which to create unique structures with specific biological functions. Examples of oligosaccharide modifications imparting biological function are currently documented, and are responsible for such functions as targeting of proteins and high affinity intermolecular interactions.; This study reveals a highly enriched source of sulfated N-linked oligosaccharides in bovine lung endothelial cells. Within this complex mixture of oligosaccharide structures is a highly negatively charged class of oligosaccharides which are unique in that they contain multiple glycosaminoglycan chains N-linked to the protein i.e. via a glucosaminyl asparagine bond. This is in contrast to more typical glycosaminoglycan chains which, with the exception of keratan sulfate type I, have only been previously found attached to the protein via a xylosyl-serine residue, O- linked. The less negatively charged species contain sialic acids, sulfates and perhaps uronic acids which collectively impart their overall negative charge.; The selectins are a family of glycoprotein receptors shown to be involved with initial events of leukocyte adhesion to endothelium. Specific oligosaccharides are the actual ligands recognized by the selectins and are critical elements of this attachment process. Aberrant interactions of the selectins and their carbohydrate ligands may lead to a variety of inflammatory disorders. The carbohydrate ligands for the selectins have been shown to contain sialic acids, and possibly sulfate groups. Therefore, we searched for selectin ligand(s) in the less negatively charged family of oligosaccharides, as well as extended previous studies on the nature of the sialic acids involved in L- and P-selectin interactions. In the process of trying to isolate additional ligands for L-selectin, we found a sub-population of endothelial heparin-like oligosaccharides which bind to L-selectin.; This dissertation discusses the isolation, characterization and comparison of these various sulfated oligosaccharides as compared with other known oligosaccharide structures.