Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains

AD Elbein - Annual review of biochemistry, 1987 - annualreviews.org
AD Elbein
Annual review of biochemistry, 1987annualreviews.org
Several recent reviews have nicely covered various aspects of the structure and
biosynthesis of the oligosaccharide chains of the N-linked or asparagine linked
glycoproteins (1-5). Therefore this introduction only breifly discusses the major pathways
that participate in the assembly of the complex, hybrid, and high-mannose types of
oligosaccharides. Inhibitors of N-linked oligosac charide formation (ie glycosylation
inhibitors and inhibitors of glycoprotein processing) have not been covered previously in this …
Several recent reviews have nicely covered various aspects of the structure and biosynthesis of the oligosaccharide chains of the N-linked or asparagine linked glycoproteins (1-5). Therefore this introduction only breifly discusses the major pathways that participate in the assembly of the complex, hybrid, and high-mannose types of oligosaccharides. Inhibitors of N-linked oligosac charide formation (ie glycosylation inhibitors and inhibitors of glycoprotein processing) have not been covered previously in this series. However, several reviews (4, 6-9) have dealt with various aspects of these inhibitors. The biosynthesis of the N-linked oligosaccharide involves the participation of lipid-linked saccharide intermediates as shown in Figure 1. In this path way, dolichyl-P serves as the carrier, and the sugars GlcNAc, mannose, and glucose are transferred from their sugar nucleotide derivatives, or from lipid-linked monosaccharides, to produce the lipid-linked oligosaccharide Glc3Man9 (GlcNAch-PP-dolichol. In the final step of this pathway, the" core" oligosacchaJide is transferred to protein while the protein is being synthesized on membrane-bound polysomes. The first step in the lipid-linked saccharide pathway, ie the transfer of GlcNAc-lP to dolichyl-P, is inhibited by
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