title: Recognition of synthetic analogues of the acceptor, beta-D-Gal p-OR, by the blood-group H gene-specified glycosyltransferase.
abstract: The acceptor-substrate specificity of a cloned alpha-(1-->2) fucosyltransferase has been explored using structural analogues of octyl beta-D-galactopyranoside (4). This monosaccharide is the minimum acceptor-substrate for the H-transferase, one of two enzymes responsible for the biosynthesis of the O blood-group antigen, which terminates in the sequence alpha-L-Fuc p-(1-->2)-beta-D-Galp. Galactoside 4 has a Km of 6 mM with this enzyme. Eighteen analogues of 4 have been prepared, including those where the hydroxyl groups at C-3, C-4, and C-6 have been replaced, independently, with deoxy, fluoro, O-methyl, amino, and acetamido functionalities. The C-3 and C-4 epimers have been prepared as has the C-5 de(hydroxymethyl)ated derivative. These compounds were screened as potential acceptors and inhibitors of the fucosyltransferase. The C-6 analogues that do not possess a charge show substrate activity with relative rates in the range of 27-316% that of 4. The C-3 modified analogues are inhibitors with estimated Ki values of 0.9-43 mM. Those analogues with modifications at C-4 were both poor inhibitors and acceptors.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: T L
authors.initials: TL
authors.lastname: Lowary
authors.forename: S J
authors.initials: SJ
authors.lastname: Swiedler
authors.forename: O
authors.initials: O
authors.lastname: Hindsgaul
mesh_terms: D000017:ABO Blood-Group System / Q000096:biosynthesis*; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005697:Galactosides / Q000737:chemistry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D013379:Substrate Specificity; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000017:ABO Blood-Group System; D005647:Fucosyltransferases; D005697:Galactosides; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C087303:octyl galactopyranoside