Synthesis of deoxy and acylamino derivatives of lactose and use of these for probing the active site of Neisseria meningitidis N-acetylglucosaminyltransferase.
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.
Westerlind
Ulrika
U
Department of Chemistry, Swedish University of Agricultural Sciences, P.O. Box 7015, S-750 07 Uppsala, Sweden.
Hagback
Per
P
Tidbäck
Björn
B
Wiik
Lotta
L
Blixt
Ola
O
Razi
Nahid
N
Norberg
Thomas
T
D001665:Binding Sites; D002240:Carbohydrate Sequence; D007785:Lactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry* / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000201:enzymology*
D015335:Molecular Probes; D017351:N-Acetylglucosaminyltransferases; C037649:N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase; D007785:Lactose