Large-scale chemical and chemo-enzymatic synthesis of a spacer-containing Pk-trisaccharide.
The Pk-trisaccharide, linked to a solid carrier, is a potential agent for neutralization of shiga-like toxin in the gastrointestinal tract. Two approaches to the multigram-scale synthesis of a linkable Pk-trisaccharide derivative were therefore investigated. A four-step chemical synthesis yielded 8-methoxycarbonyloctyl beta-lactoside in 75% yield from lactose. Further conversion of this derivative through either multistep organic synthesis or one-step enzymatic galactosylation with UDP-galactose and recombinant alpha-1,4-galactosyltransferase gave the Pk-trisaccharide derivative 8-methoxycarbonyloctyl alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside in 25% and 68% overall yields from commercial lactose, respectively.
Kamath
Vivekanand P
VP
Department of Research and Process Development, SYNSORB Biotech Inc., 201, 1204 Kensington Road Calgary, Canada AB T2E 6J7.
Yeske
Robert E
RE
Gregson
Jonathan M
JM
Ratcliffe
R Murray
RM
Fang
Ying R
YR
Palcic
Monica M
MM
D019342:Acetic Acid / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005697:Galactosides / Q000737:chemistry*; D005700:Galactosyltransferases / Q000378:metabolism; D007785:Lactose / Q000737:chemistry; D008024:Ligands; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D014312:Trisaccharides / Q000737:chemistry*; D014531:Uridine Diphosphate Galactose / Q000737:chemistry
D005697:Galactosides; D008024:Ligands; D009844:Oligosaccharides; D014312:Trisaccharides; D014531:Uridine Diphosphate Galactose; D005700:Galactosyltransferases; C045097:UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase; D007785:Lactose; D019342:Acetic Acid