title: Enzymatic synthesis of nucleobase-modified UDP-sugars: scope and limitations.
abstract: Glucose-1-phosphate uridylyltransferase in conjunction with UDP-glucose pyrophosphorylase was found to catalyse the conversion of a range of 5-substituted UTP derivatives into the corresponding UDP-galactose derivatives in poor yield. Notably the 5-iodo derivative was not converted to UDP-sugar. In contrast, UDP-glucose pyrophosphorylase in conjunction with inorganic pyrophosphatase was particularly effective at converting 5-substituted UTP derivatives, including the iodo compound, into a range of gluco-configured 5-substituted UDP-sugar derivatives in good yields. Attempts to effect 4"-epimerization of these 5-substituted UDP-glucose with UDP-glucose 4"-epimerase from yeast were unsuccessful, while use of the corresponding enzyme from Erwinia amylovora resulted in efficient epimerization of only 5-iodo-UDP-Glc, but not the corresponding 5-aryl derivatives, to give 5-iodo-UDP-Gal. Given the established potential for Pd-mediated cross-coupling of 5-iodo-UDP-sugars, this provides convenient access to the galacto-configured 5-substituted-UDP-sugars from gluco-configured substrates and 5-iodo-UTP.
authors: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
authors: Ben A
authors: BA
authors: Wagstaff
authors: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
authors: Martin
authors: M
authors: Rejzek
authors: School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK.
authors: Thomas
authors: T
authors: Pesnot
authors: King's College London, Faculty of Natural & Mathematical Sciences, Department of Chemistry, Britannia House, 7 Trinity Street, London SE1 1DB, UK.
authors: Lauren M
authors: LM
authors: Tedaldi
authors: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK; Bioorganic Chemistry and Bio-Crystallography laboratory, Faculty of Science and Technology, Free University of Bolzano, Piazza Università 5, 39100 Bolzano, Italy.
authors: Lorenzo
authors: L
authors: Caputi
authors: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
authors: Ellis C
authors: EC
authors: O'Neill
authors: Bioorganic Chemistry and Bio-Crystallography laboratory, Faculty of Science and Technology, Free University of Bolzano, Piazza Università 5, 39100 Bolzano, Italy. Electronic address: stefano.benini@unibz.it.
authors: Stefano
authors: S
authors: Benini
authors: School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK; King's College London, Faculty of Natural & Mathematical Sciences, Department of Chemistry, Britannia House, 7 Trinity Street, London SE1 1DB, UK. Electronic address: gerd.wagner@kcl.ac.uk.
authors: Gerd K
authors: GK
authors: Wagner
authors: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: rob.field@jic.ac.uk.
authors: Robert A
authors: RA
authors: Field
mesh_terms: D002236:Carbohydrate Conformation; D011756:Diphosphates / Q000737:chemistry; D044084:Erwinia amylovora / Q000201:enzymology / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism; D014534:UDPglucose 4-Epimerase / Q000378:metabolism; D014539:Uridine Diphosphate Sugars / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011756:Diphosphates; D014539:Uridine Diphosphate Sugars; C107241:diphosphoric acid; D010770:Phosphotransferases; D014534:UDPglucose 4-Epimerase
keywords: Enzymatic synthesis; Epimerase; Modified nucleobase; Pyrophosphatase; Sugar nucleotide