52885-40-2Relevant articles and documents
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.
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
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
