title: Synthesis and immunological characterization of modified hyaluronic acid hexasaccharide conjugates.
abstract: The synthesis of a tetanus toxoid (TT)-conjugate of a hyaluronic acid (HA) hexasaccharide is described. The compound was intended for use in monitoring HA levels as a disease marker and as a potential vaccine against Group A Streptococcus (GAS) infections. We also report the synthesis of a chemically modified HA-hexasaccharide-TT conjugate in which the N-acetyl moiety of the N-acetyl-D-glucosamine residue is replaced with an N-propionyl unit in order to enhance immunogenicity. The oligosaccharides are synthesized in a convergent manner. The TT-conjugate syntheses rely on the reaction of the amines on the 6-aminohexyl aglycon of the hexasaccharides with diethyl squarate to give the monoethyl squarate adducts. Subsequent reactions with lysine ε-amino groups on TT then give the glycoconjugates containing an average of 8 hexasaccharide haptens per TT molecule. Immunological studies in mice show very similar antibody responses with both conjugates, suggesting that the N-acetyl groups of the glucosaminyl residues of the HA-hexasaccharide are not a critical part of the epitope recognized by the anti-HA polyclonal immune response. Furthermore, it would appear that the N-acyl moieties are not in close contact with the amino acid residues of the antibody combining sites.
authors.affiliation: National Glycoengineering Research Center, Shandong University, Jinan 250100, PR China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Gu
authors.forename: Pal John Pal
authors.initials: PJ
authors.lastname: Adabala
authors.forename: Monica G
authors.initials: MG
authors.lastname: Szczepina
authors.forename: Silvia
authors.initials: S
authors.lastname: Borrelli
authors.forename: B Mario
authors.initials: BM
authors.lastname: Pinto
mesh_terms: D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D013291:Streptococcus / Q000187:drug effects / Q000276:immunology*; D013745:Tetanus Toxoid / Q000737:chemistry / Q000276:immunology
chemical_list: D009844:Oligosaccharides; D012709:Serum Albumin; D022541:Streptococcal Vaccines; D013745:Tetanus Toxoid; D006820:Hyaluronic Acid