title: 2',3'-Dideoxy-3'-thionucleoside triphosphates: syntheses and polymerase substrate activities.
abstract: All four 2',3'-dideoxy-3'-thio-nucleosides (ddtNTPs) function as substrates for the Y410F mutant of Deep Vent (exo-) DNA polymerase. Not only are the ddtNTPs incorporated to form the N + 1 product, but further elongations are observed in which the key step is attack of the 3'-thiol on the 5'-triphosphate. Although other polymerases are likely to differ in their use of the ddtNTPs, there does not appear to be a fundamental prohibition against using a thiol nucleophile on a phosphate anhydride electrophile. The syntheses of four ddtNTPs (C, T, A, G) are described. [structure: see text]
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
authors.lastname: Meena
authors.forename: Mui
authors.initials: M
authors.lastname: Sam
authors.forename: Kathryn
authors.initials: K
authors.lastname: Pierce
authors.forename: Jack W
authors.initials: JW
authors.lastname: Szostak
authors.forename: Larry W
authors.initials: LW
authors.lastname: McLaughlin
mesh_terms: D002384:Catalysis; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors; D010710:Phosphates / Q000737:chemistry; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013872:Thionucleosides / Q000138:chemical synthesis*
chemical_list: D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D010710:Phosphates; D013438:Sulfhydryl Compounds; D013872:Thionucleosides; C088944:Deep Vent DNA polymerase; D004259:DNA-Directed DNA Polymerase