Synthesis of deoxy and acylamino derivatives of lactose and use of these for probing the active site of Neisseria meningitidis N-acetylglucosaminyltransferase

Carbohydr Res. 2005 Feb 7;340(2):221-33. doi: 10.1016/j.carres.2004.11.017.

Abstract

Derivatives of lactose with the galactose ring substituents replaced by deoxy or acylamino functions were prepared. The 2'-, 3'-, 4'- and 6'-deoxy, 3'-acetamido and 3'-benzamido derivatives of phenyl 4-O-(beta-D-galactopyranosyl)-beta-D-glucopyranoside (phenyl beta-lactoside) were synthesized from disaccharide or monosaccharide precursors. The derivatives were tested as substrates for the N-acetylglucosaminyltransferase from Neisseria meningitidis, which uses lactosyl derivatives as acceptors and UDP-GlcNAc as the donor in a beta-(1-->3) glycosylation reaction. The 6'-deoxy derivative was nearly threefold as active as phenyl beta-lactoside, whereas the 2'- and 4'-deoxy derivatives were less active. The other derivatives were inactive, as expected.

Publication types

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

MeSH terms

  • Binding Sites
  • Carbohydrate Sequence
  • Lactose / analogs & derivatives*
  • Lactose / chemical synthesis*
  • Magnetic Resonance Spectroscopy
  • Molecular Probes / chemical synthesis*
  • Molecular Probes / chemistry
  • Molecular Sequence Data
  • Molecular Structure
  • N-Acetylglucosaminyltransferases / chemistry*
  • N-Acetylglucosaminyltransferases / metabolism*
  • Neisseria meningitidis / enzymology*

Substances

  • Molecular Probes
  • N-Acetylglucosaminyltransferases
  • N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase
  • Lactose