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Nucleic Acids Research, 1987, Vol. 15, No. 10 3997-4006
© 1987

Articles

Template-primer analogs as substrates for DNA polymerase

Thomas R. Webb*, Parkash Jhurani and Peter G. Ng

Department of Molecular Biology, Genentech, Inc. 460 Point San Bruno Boulevard, South San Francisco, CA 94080, USA

*To whom correspondence should be addressed

Received January 28, 1987. Revised April 21, 1987. Accepted April 21, 1987.

In order to gain more understanding about the mode of action of DNA polymerase, eight related partially self-complementary "hairpin" shaped oligodeoxynucleotides were prepared. Four of the oligomers contained either 1-ß-D-arabinofuranosyluracil (ara-U) or 1-ß-D-2'deoxyxylofuranosylthymine (dxT) nucleoside analogs at their 3' termini. We investigated the ability of the oligomers to prime DNA synthesis in relationship to the stability of the hybridized region, the nature of the sugar terminus and the DNA polymerase used (reverse transcriptase, or polymerase {alpha}). The results are discussed in relation to the mode of action of some nucleoside analog inhibitors of DNA polymerase. An understanding of the mechanism of DNA polymerase action was used to design template-primer analogs as polymerase inhibitors. Two of the oligodeoxynucleotide analogs prepared were found to be potent inhibitors of polymerase {alpha}.


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