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

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-(β- d-galactopyranosyl)-β- d-glucopyranoside (phenyl β-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 β-(1→3) glycosylation reaction. The 6′-deoxy derivative was nearly threefold as active as phenyl β-lactoside, whereas the 2′- and 4′-deoxy derivatives were less active. The other derivatives were inactive, as expected.