Inhibitory effects of diadenosine polyphosphates and diguanosine polyphosphates on terminal deoxynucleotidyltransferase from calf thymus.

The effects of diadenosine 5', 5"'-polyphosphates (ApnA's, n = 2-6) and diguanosine 5', 5-polyphosphates (GpnG's, n = 2-6) on the activity of terminal deoxynucleotidyltransferase (TdT) from calf thymus were investigated. Both ApnA's and GpnG's (n greater than or equal to 3) were found to inhibit TdT activity. The inhibitory effects were the strongest when TdT activity was measured by determining the incorporation of dCTP. The inhibition by ApnA's and GpnG's was due to competition with the substrate deoxynucleoside triphosphate(s). The inhibition constant (Ki) varied depending on the triphosphate substrate used, but in most cases Ki value decreased by increasing the number of the phosphoryl group of the dinucleotide inhibitors.