Chemical synthesis of the O-linked oligosaccharide of P-Selectin Glycoprotein Ligand-1
Cato, David Allen
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P-Selectin Glycoprotein Ligand-1 (PSGL-1) is the key ligand for selectins involved in the inflammatory cascade. This glycoprotein is necessary for the initial steps of the inflammation process, and the absence of this ligand from leukocytes eliminates transmigration of white blood cells into injured tissue. Also blocking P-selectins on the endothelial cell wall leads to decreases in transmigration of leukocytes. The key feature of PSGL-1 s binding to selectins is an 18 amino acid signal sequence that contains 3 tyrosine sulfate residues and a glycosylated threonine residue. This sulfated glycoprotein has been chemoenzymatically synthesized on several occasions, but has never before been completely chemically synthesized. Chemical synthesis will give this compound on a preparative scale that will allow for increased and improved biological studies on the blocking of P-selectins.