Recognition of synthetic deoxy and deoxyfluoro analogs of the acceptor alpha-L-Fuc p-(1-->2)-beta-D-Gal p-OR by the blood-group A and B gene-specified glycosyltransferases.
The disaccharide alpha-L-Fuc p-(1-->2)-beta-D-Gal p-O-(CH2)7CH3 (6), is an acceptor for both glycosyltransferases responsible for the biosynthesis of the A and B blood-group antigens. These enzymes transfer GalNAc and Gal, respectively, with an alpha-linkage to OH-3 of the Gal residue in 6. All six possible deoxy and deoxyfluoro analogs of 6, with modifications on the target Gal residue, were chemically synthesized and kinetically evaluated as both substrates and inhibitors for the A and B glycosyltransferases. Both enzymes will tolerate replacement of the hydroxyl groups at the 3 and 6 positions of the Gal residue. Substitution of OH-4 of the Gal residue, however, abolishes recognition by these glycosyltransferases. The 6-deoxy and 6-fluoro compounds are substrates for both enzymes while the 3-deoxy and 3-fluoro compounds are competitive inhibitors, with Ki values in the range 14-110 microM. Kinetic constants have been determined for the 6-deoxy and 6-fluoro derivatives.
Lowary
T L
TL
Department of Chemistry, University of Alberta, Edmonton, Canada.
Hindsgaul
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D000017:ABO Blood-Group System / Q000096:biosynthesis*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003837:Deoxy Sugars / Q000138:chemical synthesis* / Q000378:metabolism; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000378:metabolism; D009904:Optical Rotation; D013379:Substrate Specificity
D000017:ABO Blood-Group System; D003837:Deoxy Sugars; D007202:Indicators and Reagents; D009844:Oligosaccharides; D016695:Glycosyltransferases