Synthesis and glycan priming activity of acetylated disaccharides.
Five disaccharides related in structure to the glycans of vertebrate mucins have been chemically synthesized using orthogonal blocking, coupling and deblocking techniques. These include 2-naphthylmethyl 3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-( 1 --> 4)-2-acetamido-3,6-di-O-acetyl-2-deoxy-beta-D-glucopyranoside (6), 2-naphthylmethyl 2-aceta-mido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1 --> 3)-2,4,6-tri-O-acetyl-beta-D-galactopyranoside (14), 2-naph-thylmethyl2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-(1 --> 3)-2-acetamido-4,6-di- O-acetyl-2-deoxy-alpha-D-galactopyranoside (20), 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1 --> 3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside (23) and 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glu-copyranosyl-(1 --> 6)-2-acetamido-3,4-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside (27). These per-O-acetylated compounds were fed to U-937 cells to test their ability to prime oligosaccharide synthesis, inhibit glycoprotein biosynthesis and alter adhesion to E-selectin expressed on endothelial cells. The results show that 6, 14, and 20 served as substrates for oligosaccharide synthesis. The generation of glycoside-primed glycans altered the formation of glycoproteins on the cell surface and inhibited cell adhesion dependent on E-selectin.
Sarkar
A K
AK
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093, USA.
Brown
J R
JR
Esko
J D
JD
D000107:Acetylation; D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology; D009844:Oligosaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational; D000080506:Sialyl Lewis X Antigen; D013329:Structure-Activity Relationship; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism
D004187:Disaccharides; D019040:E-Selectin; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009844:Oligosaccharides; D011134:Polysaccharides; D000080506:Sialyl Lewis X Antigen; D000116:Acetylgalactosamine; D000117:Acetylglucosamine