Abstract
In the present study, effects of various 2- and 2′-substituted polyadenylic acid analogs on eukaryotic, bacterial and viral DNA polymerases were investigated. The polymer containing 2′-deoxy-2′-fluoroadenosine, (dAfl) n, showed a concentration dependent stimulation of (rA) n · (dT) 12-catalyzed reverse transcriptase reaction from Rauscher Leukemia Virus (RLV). A similar stimulation of the (rA) n · (dT) 12-catalyzed DNA polymerase-γ reaction was also observed. However, the (rC) n · (dG) 12-dependent reverse transcriptase activity was inhibited by (dAfl) n. The DNA polymerase-β activity catalyzed by (dA) n · (dT) 12 was also inhibited by (dAfl) n. The reported data indicate that (dAfl) n closely resembles (rA) n as a functional template. In contrast, the 2-substituted derivatives, poly(2-methylthioadenylic acid) and poly(2-ethylthioadenylic acid), are not able to discriminate between the reactions catalyzed by different templates. For example, both derivatives inhibit (rA) n · (dT) 12- and (rC) n · (dG) 12-catalyzed reverse transcriptase reaction to the same extent; though the methylthio derivative is a much better inhibitor than the ethylthio analog. The DNA polymerase-α was less sensitive to these inhibitors; whereas the bacterial DNA polymerase (Kornberg enzyme; DNA polymerase I) was completely resistant to the action of all the derivatives used in this study.
Published Version
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