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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Bibliographic Details
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
Format: Article
Language:English
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
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Summary: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.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol070147w