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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
Main Authors: Meena, Sam, Mui, Pierce, Kathryn, Szostak, Jack W, McLaughlin, Larry W
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Language:English
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cited_by cdi_FETCH-LOGICAL-a313t-df4d273d7936710efa876772672e14e2107f55a62932599ab309021fae4c57903
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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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