Inhibition of DNA polymerase reaction by pyrimidine nucleotide analogues lacking the 2-keto group

Guo, M. J.; Hildbrand, S.; Leumann, Christian; McLaughlin, L. W.; Waring, M. J. (1998). Inhibition of DNA polymerase reaction by pyrimidine nucleotide analogues lacking the 2-keto group. Nucleic acids research, 26(8), pp. 1863-1869. Oxford University Press 10.1093/nar/26.8.1863

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To investigate the influence of the pyrimidine 2-keto group on selection of nucleotides for incorporation into DNA by polymerases, we have prepared two C nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5-(2'-deoxy-beta-d-ribofuranosyl)pyridine-5'-triphosphate (d*CTP) and 5-(2'-deoxy- beta-d-ribofuranosyl)-3-methyl-2-pyridone-5'-triphosphate (d*TTP) respectively. Both proved strongly inhibitory to PCR catalysed by Taq polymerase; d*TTP rather more so than d*CTP. In primer extension experiments conducted with either Taq polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both nucleotides failed to substitute for their natural pyrimidine counterparts. Neither derivative was incorporated as a chain terminator. Their capacity to inhibit DNA polymerase activity may well result from incompatibility with the correctly folded form of the polymerase enzyme needed to stabilize the transition state and catalyse phosphodiester bond formation.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Leumann, Christian

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0305-1048

Publisher:

Oxford University Press

Language:

English

Submitter:

Christian Leumann

Date Deposited:

20 May 2015 11:48

Last Modified:

28 Oct 2019 13:25

Publisher DOI:

10.1093/nar/26.8.1863

Uncontrolled Keywords:

analogue analogues C-nucleosides DNA enzyme Escherichia coli Inhibition LACKING nucleoside Nucleotides PCR POLYMERASE POLYMERASE-I pyrimidine

BORIS DOI:

10.7892/boris.68609

URI:

https://boris.unibe.ch/id/eprint/68609

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