title: Thiophosphate and thiophosphonate analogues of glucose-1-phosphate: synthesis and enzymatic activity with a thymidylyltransferase.
abstract: Synthetic methods were investigated for the preparation of O and S-glucosyl thiophosphates and glucosyl 1C-thiophosphonate. Four protected glucosyl thiophosphate compounds were synthesized and characterized as precursors to glucose 1-thiophosphate. The effect of various reaction conditions and the nature of the carbohydrate and thiophosphate protecting groups and how they impact both the yields and α/β diastereoselectivity of the glucosyl thiophosphate products were explored. A novel isomerization from an O-linked to S-linked glucosyl thiophosphate was observed. α-D-Glucose-1C-thiophosphonate was synthesized and evaluated as a substrate for the thymidylyltransferase, Cps2L. Tandem mass spectrometric analysis determined the position of sulfur in the sugar nucleotide product.
authors.affiliation: Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Loranger
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Beaton
authors.forename: Katie L
authors.initials: KL
authors.lastname: Lines
authors.forename: David L
authors.initials: DL
authors.lastname: Jakeman
mesh_terms: D002236:Carbohydrate Conformation; D004789:Enzyme Activation; D005947:Glucose / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D005958:Glucosephosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013942:Thymine Nucleotides / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005958:Glucosephosphates; D010710:Phosphates; D013942:Thymine Nucleotides; C103522:deoxythymidine diphosphate-glucose; C031590:glucose-1-phosphate; D009713:Nucleotidyltransferases; C020587:glucose-1-phosphate thymidylyltransferase; D005947:Glucose; C035638:thiophosphoric acid
keywords: Glycosyl thiophosphate; Sugar nucleotide; Thiophosphonate; Thymidylyltransferase