Synthesis of GDP-5-thiosugars and their use as glycosyl donor substrates for glycosyltransferases.
Two thiopyranoside analogues of GDP-sugars, GDP-5-thio-d-mannose (14) and GDP-5-thio-l-fucose (15), were synthesized. The syntheses included the phosphorylations of tetra-O-acetyl-5-thio-d-mannosyl bromide (4) and tri-O-benzoyl-l-fucosyl bromide (6) with silver dibenzyl phosphate, deprotection of the phosphate groups, and condensation of the deprotected phosphates with GMP-imidazolidate (13) in the presence of MgCl(2). These GDP-sugar analogues were found to be donor substrates for alpha(1,2)mannosyltransferase and alpha(1,3)fucosyltransferase, affording a 5-thiomannose-containing disaccharide (18) and a 5-thiofucose-containing trisaccharide (21), respectively. The conformation of the disaccharide analogue 18 was similar to that of its native counterpart by ROESY. These findings for GDP-5-thiosugars together with previous demonstrations of enzymatic transfer from UDP-5-thiosugars will allow the production of panels of oligosaccharide analogues with hydrolase-resistant properties.
Tsuruta
Osamu
O
Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Yuasa
Hideya
H
Hashimoto
Hironobu
H
Sujino
Keiko
K
Otter
Albin
A
Li
Hong
H
Palcic
Monica M
MM
D002240:Carbohydrate Sequence; D002855:Chromatography, Thin Layer; D004187:Disaccharides / Q000138:chemical synthesis; D019075:Electrophoresis, Capillary; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000737:chemistry*; D014312:Trisaccharides / Q000138:chemical synthesis
D004187:Disaccharides; D007202:Indicators and Reagents; D013865:Thioglycosides; D014312:Trisaccharides; D006153:Guanosine Diphosphate; D016695:Glycosyltransferases