Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates.

Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates. Research Abstract Details 

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Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates. Abstract Text:

Shuhei Imoto,Jennifer N Patro,Yu Lin Jiang,Natsuhisa Oka,Marc M Greenberg,

The nucleoside triphosphates of N6-(2-deoxy-alpha,beta-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy.dGTP) and its C-nucleoside analogue (beta-C-Fapy.dGTP) were synthesized. The lability of the formamide group required that nucleoside triphosphate formation be carried out using an umpolung strategy in which pyrophosphate was activated toward nucleophilic attack. The Klenow fragment of DNA polymerase I from Escherichia coli accepted Fapy.dGTP and beta-C-Fapy.dGTP as substrates much less efficiently than it did dGTP. Subsequent extension of a primer containing either modified nucleotide was less affected compared to when the native nucleotide is present at the 3'-terminus. The specificity constants are sufficiently large that nucleoside triphosphate incorporation could account for the level of Fapy.dG observed in cells if 1% of the dGTP pool is converted to Fapy.dGTP. Similarly, polymerase-mediated introduction of beta-C-Fapy.dG could be useful for incorporating useful amounts of this nonhydrolyzable analogue for use as an inhibitor of base excision repair. The kinetic viability of these processes is enhanced by inefficient hydrolysis of Fapy.dGTP and beta-C-Fapy.dGTP by MutT, the E. coli enzyme that releases pyrophosphate and the corresponding nucleoside monophosphate upon reaction with structurally related nucleoside triphosphates.

Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates. Publishing Authors By Initials

S Imoto,JN Patro,YL Jiang,N Oka,MM Greenberg,

For similar heterocyclic compounds: heterocyclic compounds, 1-ring: pyrimidines research abstracts see: heterocyclic compounds: heterocyclic compounds, 1-ring: pyrimidines research

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Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of the American Chemical Society

VOLUME: 128

Page Numbers: 14606-11

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 15

MONTH: Nov

YEAR: 2006

Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates. Keywords Mesh Terms:

KEYWORDS: Pyrimidines

MESH TERMS: chemistry

Chemical & Substance for Abstract: Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates. Information

Substance Name: DNA-Directed DNA Polymerase

Registry Number: EC 2.7.7.7

Grant and Affiliation Information for Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates.

AFFILIATION: Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA074954-09

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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