title: Synthesis and glycan priming activity of acetylated disaccharides.
abstract: 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.
authors: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093, USA.
authors: A K
authors: AK
authors: Sarkar
authors: J R
authors: JR
authors: Brown
authors: J D
authors: JD
authors: Esko
mesh_terms: 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
chemical_list: D004187:Disaccharides; D019040:E-Selectin; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009844:Oligosaccharides; D011134:Polysaccharides; D000080506:Sialyl Lewis X Antigen; D000116:Acetylgalactosamine; D000117:Acetylglucosamine