Synthesis and characterization of an anomeric sulfur analogue of CMP-sialic acid.
alpha-2,3-Sialyltransferase catalyzes the transfer of sialic acid from CMP-sialic acid (1) to a lactose acceptor. An analogue of 1 was synthesized in which the anomeric oxygen atom was replaced with a sulfur atom (1S). The key step in the synthesis of 1S was a tetrazole-promoted coupling of a cytidine-5'-phosphoramidite with a glycosyl thiol of a protected sialic acid. Compounds 1 and 1S were characterized for their activity in a sialyl transfer assay. The rate of solvolysis in aqueous buffer of analogue 1S was 50-fold slower than that of 1. Analogue 1S was found to be substrate for alpha-2,3-sialyltransferase. The K(m) of 1S was just 3-fold higher than that of 1, while the k(cat) of 1S was 2 orders of magnitude lower compared to 1.
Cohen
S B
SB
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.
Halcomb
R L
RL
D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D012799:Sialyltransferases / Q000737:chemistry; D012997:Solvents; D013455:Sulfur / Q000737:chemistry; D013816:Thermodynamics; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D012794:Sialic Acids; D012997:Solvents; D013455:Sulfur; D012799:Sialyltransferases; D003568:Cytidine Monophosphate; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase