52885-40-2Relevant academic research and scientific papers
Synthesis, conformation and T-helper cell stimulation of an O-linked glycopeptide epitope containing extended carbohydrate side-chains
Cudic, Mare,Ertl, Hildegund C.J.,Otvos Jr., Laszlo
, p. 3859 - 3870 (2007/10/03)
To answer the question whether or not T cells to immunodominant protein fragments recognize glycosylated antigens, we synthesized a series of glycopeptides corresponding to peptide 31D, a major T-helper cell epitope of the rabies virus nucleoprotein. Thr4 of the epitope is known to allow mono- or disaccharide side-chain substitutions in either α- or β-anomeric configuration without interfering with MHC-binding. To model naturally occurring glycoprotein fragments that carry extended sugar chains, we prepared Fmoc-Ser/Thr-OPfp building blocks containing α- and β-linked linear tri- and heptasaccharides. Peptide 31D was synthesized with the complex carbohydrates attached to Thr4, and the T-helper cell activity of the glycopeptides was determined. Addition of α-linked carbohydrates, that mimic most of the natural O-linked glycoproteins, resulted in a major drop in the T-cell stimulatory ability in a sugar length-dependent manner. In contrast, the cytosolic glycoprotein mimicking β-linked glycopeptides retained their T-cell stimulatory activity, with the trisaccharide-containing analogue being almost as potent as the unglycosylated peptide. When the peptides were preincubated with diluted human serum, all peptides lost their ability to stimulate the 9C5.D8-H hybridoma. These findings indicated that (i) in contrast to cytosolic glycosylation, incorporation of long O-linked carbohydrates into T-helper cell epitopes abrogates the antigenicity of these protein fragments, and (ii) glycosylation is not a viable alternative to improve the immunogenic properties of subunit peptide vaccines. Glycosylation with all four carbohydrate moieties similarly destroyed the inducible α-helical structure of peptide 31D as detected by CD, indicating that the differences in the T-cell activity were not due to different peptide conformations.
Synthesis and conformational analysis of the T-antigen disaccharide (β-D-Gal-(1←3)-α-D-GalNAc-OMe)
Bukowski, Ralph,Morris, Laura M.,Woods, Robert J.,Weimar, Thomas
, p. 2697 - 2705 (2007/10/03)
We report an improved synthesis of the T-antigen disaccharide [β-D-Gal-(1←3)-α-D-GalNAc-OMe], incorporating recycling of the undesired β-glycosyl acceptor [methyl 2-azido-4,6-benzylidene-2-deoxy-β-D-galactopyranoside (9β)] through anomerization by treatment with FeCl3. The conformational analysis of the disaccharide made use of high quality NOE data in combination with extensive Metropolis Monte-Carlo (MMC) and molecular dynamic (MD) simulations. To sample the conformational space sufficiently, 9.5·106 Monte-Carlo steps were collected for the MMC simulations, while the fully solvated MD simulations were performed for 10 ns for comparison. In general, the MMC and MD simulations agreed very well. Comparison of theoretical NOE curves from both MMC and MD simulations with the experimental curves showed that the disaccharide populates two regions of conformational space, with a population of about 95% for the global minimum energy region and about 5% for a local minimum energy region.
Crystallographic studies of some cyclic benzylidene acetals: Key synthons for o-glycoamino acid building blocks and solid-phase oligosaccharide synthesis
Gururaja, Tarikere L.,Venugopalan, Paloth,Levine, Michael J.
, p. 747 - 759 (2007/10/03)
Synthesis of methyl 2-azido-2-deoxy-4,6-O-benzylidene-β-D-galactopyranoside (1), one of the key components in the synthesis of O-glycoamino acids, was undertaken in order to synthesize Tn and TF(3) antigen building blocks. In pursuit of an alternative app
SYNTHESIS OF DISACCHARIDE FRAGMENTS OF DERMATAN SULFATE
Marra, Alberto,Dong, Xia,Petitou, Maurice,Sinay, Pierre
, p. 39 - 50 (2007/10/02)
Condensation of crystalline methyl 2-azido-4,6-O-benzylidene-2-deoxy-β-D-galactopyranoside with methyl (2,3,4-tri-O-acetyl-α-L-idopyranosyl bromide)uronate in dichloromethane, in the presence of silver triflate and molecular sieve, provided 54 percent of
LEWISSAEURE-KATALYSIERTE SYNTHESEN VON DI- UND TRI-SACCHARID-SEQUENZEN DER O- UND N-GLYCOPROTEINE, ANWENDUNG VON TRIMETHYLSILYLTRIFLUOROMETHANESULFONAT
Paulsen, Hans,Paal, Michael
, p. 53 - 70 (2007/10/02)
In the presence of trimethylsilyltrifluoromethanesulfonate as Lewis acid catalyst, β-acetates reacted, as glycosyl donors and with neighboring-group participation, with secondary hydroxyl groups of saccharides having low reactivity to give β-glycosidicall
