The focus of this research will be the development of strategies for engineering homogeneous glycoforms on proteins and cells using the principle of chemoselective ligation. For gycoprotein engineering, a three-step process is envisioned. First, recombinant expression of O-linked glycoproteins in the presence of an oligosaccharide elongation inhibitor yields truncated glycoproteins with single GalNAc residues at the O-linked sites. Second, an aldehyde group is introduced onto truncated glycoproteins using galactose oxidase. Third, synthetic oligosaccharides functionalized with complementary reactive groups are ligated onto the truncated scaffold, affording glycoproteins with rationally designed, homogeneous glycoforms. The focus of the educational activities involves course and web site development. With this Faculty Early Development (CAREER) award, the Organic and Macromolecular Chemistry Program is supporting the research and educational activities of Dr. Carolyn Bertozzi of the Department of Chemistry at the University of California, Berkeley. Professor Bertozzi will focus her research efforts on developing strategies for engineering homogeneous glycoforms on proteins and cells using the techniques of synthetic chemistry, recombinant expression and metabolic engineering. This approach will be used to investigate glycoproteins involved in leukocyte activation and cell-cell interactions essential to the inflammatory response. Course and curriculum development will be stressed in the educational efforts supported by the award.
