1220958-06-4Relevant academic research and scientific papers
Synthesis and immunological characterization of modified hyaluronic acid hexasaccharide conjugates
Gu, Guofeng,Adabala, Pal John Pal,Szczepina, Monica G.,Borrelli, Silvia,Pinto, B. Mario
, p. 8004 - 8019 (2013/09/12)
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.
Convergent syntheses of LeX analogues
Wang, An,Hendel, Jenifer,Auzanneau, France-Isabelle
supporting information; experimental part, (2010/07/18)
The synthesis of three Lex derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N-acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40 °C under excess of BF3·OEt2 activation and proceeded best if the acceptor carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Lex trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6-acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70-95%). In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led respectively to the n-hexyl and 6-aminohexyl trisaccharide targets. Unexpectedly, the 6-acetylthiohexyl analogue underwent desulfurization and gave the n-hexyl glycoside product, whereas the 6-benzylthiohexyl analogue gave the desired disulfide trisaccharide dimer. This study constitutes a particularly efficient and convergent preparation of these three Lex analogues.
