Differential inhibition of various deoxyribonucleic and ribonucleic acid polymerases by suramin

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Abstract
The inhibitory effects of hexasodium sym‐bis(m‐aminobenzoyl‐m‐amino‐p‐methylbenzoyl‐1‐naphthylamino‐4,6,8‐trisulfonate)carbamide (trivial name: suramin) on the activities of various deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) polymerases from mammalian cells, bacteria and retrovirus were examined and compared with each other. Among the various DNA and RNA polymerases tested, the activities of DNA primase, DNA polymerase α, reverse transcriptase and Escherichia coli RNA polymerase were strongly inhibited by suramin, while the activities of other enzymes including DNA polymerases β and γ, terminal deoxynucleotidyl‐transferase and DNA polymerase I were relatively resistant to inhibition by this drug. The inhibition by suramin of DNA polymerase α from KB cells and Rauscher murine leukemia virus (RLV) reverse transcriptase was due to competition with the respective template · primer (activated DNA for α polymerase and (rA)n· (dT)12–18 for reverse transcriptase) for the template · primer‐binding site of the enzyme, while the inhibition of DNA primase and E. coli RNA polymerase was due to competition with the ribonucleoside triphosphate substrate. The inhibition constants (Ki) of suramin were determined to be 2.6 μM, 0.35 μM, 0.54 μM and 0.70 μM for DNA primase, DNA polymerase α, RLV reverse transcriptase and E. coli RNA polymerase respectively. The observed inhibitions of these polynucleotide‐synthesizing enzymes by suramin seem to explain, at least in part, an as yet unknown mechanism of trypanocidal action of this drug.