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2‘,3‘-Dideoxy-3‘-thionucleoside Triphosphates: Syntheses and Polymerase Substrate Activities
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‘-triphos...
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Published in: | Organic letters 2007-03, Vol.9 (6), p.1161-1163 |
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creator | Meena Sam, Mui Pierce, Kathryn Szostak, Jack W McLaughlin, Larry W |
description | 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. |
doi_str_mv | 10.1021/ol070147w |
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source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
subjects | Catalysis DNA-Directed DNA Polymerase - metabolism Electrophoresis, Polyacrylamide Gel Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology Mutation Nucleic Acid Synthesis Inhibitors Phosphates - chemistry Substrate Specificity Sulfhydryl Compounds - chemistry Thionucleosides - chemical synthesis |
title | 2‘,3‘-Dideoxy-3‘-thionucleoside Triphosphates: Syntheses and Polymerase Substrate Activities |
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