230286-11-0Relevant articles and documents
Chemoenzymatic synthesis of 2-azidoethyl-ganglio-oligosaccharides GD3, GT3, GM2, GD2, GT2, GM1, and GD1a
Blixt, Ola,Vasiliu, Daniela,Allin, Kirk,Jacobsen, Nathan,Warnock, Dawn,Razi, Nahid,Paulson, James C.,Bernatchez, Stephane,Gilbert, Michel,Wakarchuk, Warren
, p. 1963 - 1972 (2005)
We have synthesized several ganglio-oligosaccharide structures using glycosyltransferases from Campylobacter jejuni. The enzymes, α-(2→3/8)-sialyltransferase (Cst-II), β-(1→4)-N- acetylgalactosaminyltransferase (CgtA), and β-(1→3)- galactosyltransferase (CgtB), were produced in large-scale fermentation from Escherichia coli and further characterized based on their acceptor specificities. 2-Azidoethyl-glycosides corresponding to the oligosaccharides of GD3 (α-D-Neup5Ac-(2→8)-α-D-Neup5Ac-(2→3)-β-D-Galp- (1→4)-β-D-Glcp-), GT3 (α-D-Neup5Ac-(2→8)-α-D-Neup5Ac- (2→8)-α-D-Neup5Ac-(2→3)-β-D-Galp-(1→4)-β-D-Glcp-) , GM2 (β-D-GalpNAc-(1→4)-[α-D-Neup5Ac-(2→3)]-β-D-Galp- (1→4)-β-D-Glcp-), GD2 (β-D-GalpNAc-(1→4)-[α-D-Neup5Ac- (2→8)-α-D-Neup5Ac-(2→3)]-β-D-Galp-(1→4) -β-D-Glcp-), GT2 (β-D-GalpNAc-(1→4)-[α-D-Neup5Ac-(2→8) -α-D-Neup5Ac-(2→8)-α-D-Neup5Ac-(2→3)]-β-D-Galp- (1→4)-β-D-Glcp-), and GM1 (β-D-Galp-(1→3)-β-D-GalpNAc- (1→4)-[α-D-Neup5Ac-(2→3)]-β-D-Galp-(1→4) -β-D-Glcp-) were synthesized in high yields (gram-scale). In addition, a mammalian α-(2→3)-sialyltransferase (ST3Gal I) was used to sialylate GM1 and generate GD1a (α-D-Neup5Ac-(2→3)-β-D-Galp-(1→3)- β-D-GalpNAc-(1→4)-[α-D-Neup5Ac-(2→3)]-β-D-Galp- (1→4)-β-D-Glcp-) oligosaccharide. We also cloned and expressed a rat UDP-N-acetylglucosamine-4′epimerase (GalNAcE) in E. coli AD202 cells for cost saving in situ conversion of less expensive UDP-GlcNAc to UDP-GalNAc.
The trans-sialidase from Trypanosoma cruzi efficiently transfers α-(2→3)-linked N-glycolylneuraminic acid to terminal β-galactosyl units
Agusti, Rosalia,Giorgi, Maria Eugenia,de Lederkremer, Rosa M.
, p. 2465 - 2469 (2007)
The trans-sialidase from Trypanosoma cruzi (TcTS), the agent of Chagas' disease, is a unique enzyme involved in mammalian host-cell invasion. Since T. cruzi is unable to synthesize sialic acids de novo, TcTS catalyzes the transfer of α-(2→3)-sialyl residues from the glycoconjugates of the host to terminal β-galactopyranosyl units present on the surface of the parasite. TcTS also plays a key role in the immunomodulation of the infected host. Chronic Chagas' disease patients elicit TcTS-neutralizing antibodies that are able to inhibit the enzyme. N-Glycolylneuraminic acid has been detected in T. cruzi, and the trans-sialidase was pointed out as the enzyme involved in its incorporation from host glycoconjugates. However, N-glycolylneuraminic acid α-(2→3)-linked-containing oligosaccharides have not been analyzed as donors in the T. cruzi trans-sialidase reaction. In this paper we studied the ability of TcTS to transfer N-glycolylneuraminic acid from Neu5Gc(α2→3)Gal(β1→4)GlcβOCH2CH2N3 (1) and Neu5Gc(α2→3)Gal(β1→3)GlcNAcβOCH2CH2N3 (2) to lactitol, N-acetyllactosamine and lactose as acceptor substrates. Transfer from 1 was more efficient (50-65%) than from 2 (20-30%) for the three acceptors. The reactions were inhibited when the enzyme was preincubated with a neutralizing antibody. Km values were calculated for 1 and 2 and compared with 3′-sialyllactose using lactitol as acceptor substrate. Analysis was performed by high-performance anion-exchange (HPAEC) chromatography. A competitive transfer reaction of compound 1 in the presence of 3′-sialyllactose and N-acetyllactosamine showed a better transfer of Neu5Gc than of Neu5Ac.
The design and synthesis of an α-Gal trisaccharide epitope that provides a highly specific anti-Gal immune response
Anraku, Kensaku,Sato, Shun,Jacob, Nicholas T.,Eubanks, Lisa M.,Ellis, Beverly A.,Janda, Kim D.
, p. 2979 - 2992 (2017/04/10)
Carbohydrate antigens displaying Galα(1,3)Gal epitopes are recognized by naturally occurring antibodies in humans. These anti-Gal antibodies comprise up to 1% of serum IgG and have been viewed as detrimental as they are responsible for hyperacute organ rejections. In order to model this condition, α(1,3)galactosyltransferase-knockout mice are inoculated against the Galα(1,3)Gal epitope. In our study, two α-Gal trisaccharide epitopes composed of either Galα(1,3)Galβ(1,4)GlcNAc or Galα(1,3)Galβ(1,4)Glc linked to a squaric acid ester moiety were examined for their ability to elicit immune responses in KO mice. Both target epitopes were synthesized using a two-component enzymatic system using modified disaccharide substrates containing a linker moiety for coupling. While both glycoconjugate vaccines induced the required high anti-Gal IgG antibody titers, it was found that this response had exquisite specificity for the Galα(1,3)Galβ(1,4)GlcNAc hapten used, with little cross reactivity with the Galα(1,3)Galβ(1,4)Glc hapten. Our findings indicate that while homogenous glycoconjugate vaccines provide high IgG titers, the carrier and adjuvanting factors can deviate the specificity to an antigenic determinant outside the purview of interest.
MODULAR SYNTHESIS OF AMPHIPHILIC JANUS GLYCODENDRIMERS AND THEIR SELF-ASSEMBLY INTO GLYCODENDRIMERSOMES
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Paragraph 00132, (2014/12/12)
The invention concerns compounds of the formula (I) wherein: Y1 and Y2 are independently a monosaccharide or disaccharide; X1 and X2 are independently -(R9-O)m-, -(R10)P-, -O-(R11-O)q-, -R16-O-R17-O- or a covalent bond; Q1 and Q2 are independently a nitrogen-containing heterocycle moiety; Z1 and Z2 are independently -(O-R7)-, -(O-C(=O)-R8)a-, -O-C(=O)-R12-C(=0)-R13-, -O- C(=O)-R14-C(=O)-R15 or a covalent bond; R7-R17 are each independently C1-C6 alkyl; R1-R6 are each independently a linear or branched alkly group; b, c, d, e, f, and g are 0 or 1, provided b + c + d equals at least 2 and e + f + g equals at least 2; and a, m, p, and q are each an integer from 1-6.