Combined thioether/hydrazone chemoselective ligation reactions for the synthesis of glycocluster-antigen peptide conjugates.
Hydrazone/thioether ligation reactions show promise for the synthesis of clustered glycosides-antigen conjugates. Due to its propensity to aggregate, tetanus toxoid-derived epitopic peptide TT(830-846) was elected to further evaluate this three-component ligation process. This difficult sequence was supplemented by a hydrazine or a glyoxylyl group either at its C- or N-terminus. The peptide-hydrazines or peptide-aldehydes thus obtained were coupled with glyoxylyl- (or hydrazino-) N-chloroacetylated-L-lysinyl trees and 2-thioethyl-alpha-D-mannopyranoside. As anticipated the ligations were controlled by the nature of the peptide and proved difficult for the C-terminal aldehyde derivative. However, when the process was performed in absence of buffer and using mannitol as a dispersing agent, all combinations finally led to the expected glycoconjugates in 40-60% purified yields.
Grandjean
Cyrille
C
SEDAC-Therapeutics, Parc Eurasanté - Le Galenis, Bâtiment B, 85, rue Nelson Mandela, 59120 Loos, France. Cyrille.Grandjean@sedac-therapeutics.com
Santraine
Valérie
V
Fruchart
Jean-Sébastien
JS
Melnyk
Oleg
O
Gras-Masse
Hélène
H
D000595:Amino Acid Sequence; D000941:Antigens / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D006001:Glycoconjugates / Q000138:chemical synthesis*; D006835:Hydrazones / Q000737:chemistry; D009842:Oligopeptides / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry; D013745:Tetanus Toxoid / Q000737:chemistry
D000941:Antigens; D006001:Glycoconjugates; D006835:Hydrazones; D009842:Oligopeptides; D010446:Peptide Fragments; D013440:Sulfides; D013745:Tetanus Toxoid; C093151:tetanus toxoid (830-843)