Chemo-enzymatic synthesis of C-9 acetylated sialosides.
A chemo-enzymatic synthesis of [(5-acetamido-9-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonic acid)-(2-->3)-O-(beta-D-galactopyranosyl)-(1-->3)-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)]-l-serine acetate (1) has been accomplished by a regioselective chemical acetylation of Neu5Ac (2) to give 9-O-acetylated sialic acid 3, which was enzymatically converted into CMP-Neu5,9Ac(2) (4) employing a recombinant CMP-sialic acid synthetase from Neisseria meningitis [EC 2.7.7.43]. The resulting compound was then employed for the enzymatic glycosylation of the C-3' hydroxyl of chemically prepared glycosylated amino acid 10 using recombinant rat alpha-(2-->3)-O-sialyltransferase expressed in Spodooptera frugiperda [EC 2.4.99.4] to give, after deprotection of the N(alpha)-benzyloxycarbonyl (CBz)-protecting group of serine, target compound 1. The N(alpha)-CBz-protected intermediate 11 can be employed for the synthesis of glycolipopeptides for immunization purposes.
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Jana
J
Rauvolfova
Andre
A
Venot
Geert-Jan
GJ
Boons
D000818:Animals; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019158:N-Acetylneuraminic Acid / Q000138:chemical synthesis*; D000216:N-Acylneuraminate Cytidylyltransferase / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D012799:Sialyltransferases; D000216:N-Acylneuraminate Cytidylyltransferase; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase