Recognition of synthetic analogues of the acceptor, β- d-Gal p-OR, by the blood-group H gene-specified glycosyltransferase

• Published in: Carbohydrate research 1994-04, Vol.256 (2), p.257-273
• Main Authors: Lowary, Todd L., Swiedler, Stuart J., Hindsgaul, Ole
• Format: Article
• Language: English
• Subjects: ABO Blood-Group System - biosynthesis; Carbohydrate Sequence; Cloning, Molecular; Fucosyltransferases - antagonists & inhibitors; Fucosyltransferases - metabolism; Galactoside 2-alpha-L-fucosyltransferase; Galactosides - chemistry; Models, Chemical; Molecular Sequence Data; Sequence Analysis; Substrate Specificity
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/0008-6215(94)84212-4

The acceptor-substrate specificity of a cloned α-(1 → 2) fucosyltransferase has been explored using structural analogues of octyl β- 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 λ- l-Fuc p-(1 → 2)-β- d-Gal p. Galactoside 4 has a K m 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 K i values of 0.9-43 mM. Those analogues with modifications at C-4 were both poor inhibitors and acceptors.