Polymer-supported and chemoenzymatic synthesis of the Neisseria meningitidis pentasaccharide: a methodological comparison.
Neisseria meningitidis trisaccharide [GlcNAc[(1-->3)Galbeta(1-->4)Glc-R], tetrasaccharide [Galbeta(1-->4)GlcNAcbeta(1--> 3)Galbeta(1-->4)Glc-R], and a pentasaccharide [Neu5Acalpha(2-->3)Galbeta(1-->4)GlcNAcbeta(1-->3)G albeta(1-->4)Glc-SPh] were prepared via conventional chemical synthesis, polymer-supported synthesis, and chemoenzymatic methods, starting from D-lactose. The polymer polyethyleneglycol monomethylether (MPEG) and the linker dioxyxylene (DOX) were used with a lactose-bound acceptor to improve the purification process. Several enzymes (LgtA, GalE-LgtB fusion, and CMP-Neu5Ac synthetase/sialyltransferase fusion) were used for syntheses of these oligosaccharides. Excellent stereo- and regioselectivities as well as high yield (> 90% from Gal(1-->4)Glc-SPh) of the pentasaccharide were obtained. Both of the convenient processes are suitable for efficient preparation of target oligosaccharides.
Yan
F
F
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ont.
Wakarchuk
W W
WW
Gilbert
M
M
Richards
J C
JC
Whitfield
D M
DM
D000942:Antigens, Bacterial / Q000737:chemistry*; D001426:Bacterial Proteins; D002240:Carbohydrate Sequence; D016695:Glycosyltransferases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009345:Neisseria meningitidis / Q000737:chemistry* / Q000472:pathogenicity; D009844:Oligosaccharides / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; C023023:lipid-linked oligosaccharides; D016695:Glycosyltransferases; C401409:LgtA protein, bacteria; D017351:N-Acetylglucosaminyltransferases; D012799:Sialyltransferases