Chemoenzymatic Synthesis of Sialosides and Their Applications

Abstract

Recent progress in the development of efficient one-pot three-enzyme chemoenzymatic synthesis and application of functionalized sialosides is described. By taking the advantage of relaxed substrate specificity of several bacterial sialoside biosynthetic enzymes, the method has been used for the prepactive scale synthesis of a2,3- and α2,6-linked sialoside libraries containing naturally and non-naturally occurring sialic acid modifications. Starting from the hexose precursors (ManNAc or mannose) of sialic acids, a library of pNP-tagged sialyl disaccharides with various naturally occurring sialic acid forms, different sialyl linkages, and different penultimate monosaccharides have also been prepared and used in the substrate specificity studies of bacterial sialidases in a 96-well plate-based colorimetric high-throughput screening platform. The combination of efficient chemoenzymatic synthesis and high-throughput screening is a powerful approach to studying proteins that recognizing sialic acid-containing carbohydrates.