One focus of this research is the development of new methods for the solid-phase synthesis of glycosylated ribonuclease A using an engineered subtilisin and glycosyltransferase as catalysts. The second focus is the development of simple and conformationally constrained mimetics of sialyl Lewis X, a tetrasaccharide ligand binding to E- and P-selectin during inflammatory reactions and metastasis, with improved stability toward enzymatic hydrolysis and higher affinity than the parent ligand for the receptor. With this renewal award, the Synthetic Organic Program is supporting the research of Dr. Chi-Huey Wong of the Department of Chemistry at the Scripps Research Institute. Professor Wong will focus his work on developing new and practical chemo-enzymatic methods for the synthesis of glycoproteins and complex carbohydrate mimetics in order to study the effects of carbohydrates on protein structure and function, to probe carbohydrate-receptor interaction and to exploit carbohydrate-based therapeutic potential.
