Synthesis of a disialylated hexasaccharide of type VIII group B Streptococcus capsular polysaccharide.
As part of our program to design, develop and prepare protective vaccines against the bacterial pathogens Group B Streptococcus, we report the synthesis of a disialylated hexasaccharide. This hexasaccharide represents a portion of the serotype-specific capsular polysaccharide of Type VIII that has the tetrasaccharide repeat unit [beta-L-Rhap-(1-->4)-beta-D-Glcp-(1-->4)-[alpha-Neu5Ac-(2--> 3)]-beta-D- Galp-(1-->4)]n. A tetrasaccharide corresponding to this repeat unit has been synthesized by us [E. Eichler, H.J. Jennings, D.M. Whitfield, J. Carbohydr. Chem., 16 (1997) 385-411]. Since the protective epitopes are believed to involve several repeat units, methods to extend this tetrasaccharide were examined. This objective requires a glycosylation of the unreactive OH-4 of the beta-L-Rhap, which was accomplished by coupling a D-Galp glycosyl trichloroacetimidate donor with a beta-L-Rhap-(1-->4)-D-Glcp acceptor. Subsequent coupling of this trisaccharide as a donor to an alpha-Neu5Ac-(2-->3)-D-Galp disaccharide acceptor gave a pentasaccharide. The pentasaccharide was deprotected and enzymatically sialylated using an alpha-(2-->3)-sialyltransferase from Campylobacter jejuni to give the title hexasaccahride alpha-Neu5Ac-(2-->3)- beta-D-Galp-(1-->4)-beta-L-Rhap-(1-->4)-beta-D-Glcp-(1-->4)-[alpha -Neu5Ac- (2-->3)]-beta-D-Galp-(1-->O)-(CH2)3N3.
Eichler
E
E
National Research Council, Ottawa, Ontario, Canada.
Jennings
H J
HJ
Gilbert
M
M
Whitfield
D M
DM
D016667:Bacterial Capsules; D001428:Bacterial Vaccines; D002240:Carbohydrate Sequence; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D012794:Sialic Acids / Q000138:chemical synthesis*; D013292:Streptococcus agalactiae
C401408:3-azidopropyl (5-acetamido-3,5-dideoxy-2-nonulopyranosylonic acid)-2-3-galactopyranosyl-1-4-rhamnopyranosyl-1-4-glucopyranosyl-1-4-(5-acetamido-3,5-nonulopyranosylonic acid-2-3)galactopyranoside; D001428:Bacterial Vaccines; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; D012794:Sialic Acids