Synthesis and characterization of an anomeric sulfur analogue of CMP-sialic acid

J Org Chem. 2000 Sep 22;65(19):6145-52. doi: 10.1021/jo000646+.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbohydrate Sequence
  • Chromatography, High Pressure Liquid
  • Cytidine Monophosphate / analogs & derivatives*
  • Cytidine Monophosphate / chemical synthesis*
  • Cytidine Monophosphate / chemistry
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Sialic Acids / chemical synthesis*
  • Sialic Acids / chemistry
  • Sialyltransferases / chemistry
  • Solvents
  • Sulfur / chemistry
  • Thermodynamics
  • beta-Galactoside alpha-2,3-Sialyltransferase

Substances

  • Sialic Acids
  • Solvents
  • Sulfur
  • Sialyltransferases
  • Cytidine Monophosphate
  • beta-Galactoside alpha-2,3-Sialyltransferase