11] Inhibitors of glycoprotein synthesis

Abstract

This chapter focuses on the inhibitors of glycoprotein synthesis. Tunicamycin is a nucleoside antibiotic produced by Streptomyces lysosuperificus . This antibiotic has shown to inhibit the first reaction in the lipid-linked saccharide pathway—that is, the transfer of GlcNAc-1-P from UDP-GIcNAc to dolichyl-P to form dolichyl-pyrophosphoryl-GlcNAc. This GlcNAc-lipid serves as the acceptor for the remaining sugars to produce the Glc 3 Man 9 GlcNAc 2 -pyrophosphoryl-dolichol that is the ultimate donor of oligosaccharide to protein. In the presence of sufficient amounts of tunicamycin, this lipid-linked oligosaccharide cannot be formed and the protein is not glycosylated. Several other antibiotics have been described that are closely related in structure to tunicamycin and have the same site of action. These include streptovirudin, mycospocidin, antibiotic 24010, and antibiotic MM 19290. Although these compounds have not been characterized to the same extent as tunicamycin, the method of purification and their chromatographic properties are quite similar to those of tunicamycin.