title: Branch-specific sialylation of IgG-Fc glycans by ST6Gal-I.
abstract: Sialylated forms of the Fc fragment of immunoglobulin G, produced by the human alpha2-6 sialyltransferase ST6Gal-I, were identified as potent anti-inflammatory mediators in a mouse model of rheumatoid arthritis and are potentially the active components in intravenous IgG anti-inflammatory therapies. The activities and specificities of hST6Gal-I are, however, poorly characterized. Here MS and NMR methodology demonstrates glycan modification occurs in a branch-specific manner with the alpha1-3Man branch of the complex, biantennary Fc glycan preferentially sialylated. Interestingly, this substrate preference is preserved when using a released glycan, suggesting that the apparent occlusion of glycan termini in Fc crystal structures does not dominate specificity.
authors.affiliation: Complex Carbohydrate Research Center, 315 Riverbend Road, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Barb
authors.forename: Evan K
authors.initials: EK
authors.lastname: Brady
authors.forename: James H
authors.initials: JH
authors.lastname: Prestegard
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008958:Models, Molecular; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism*; D013379:Substrate Specificity; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D000893:Anti-Inflammatory Agents; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011134:Polysaccharides; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase