Table 3.
HCV NS5B nucleoside and nucleoside analog ATP-mediated excision
Shown is a summary of kinetic parameters for ATP-meditated excision of incorporated nucleosides and nucleoside analogs. The rate constants were derived by fitting the data sets using Scheme 2. S.E. values were derived by nonlinear regression in globally fitting the data (19). The individual rates for the reverse reactions are not defined by the data, and therefore only the specificity constant (k−5/K6) is able to be determined.
Nucleotide | 1/K4 | k5 | K4k5 × 10−6 | k−5/K6 |
---|---|---|---|---|
μm | s−1 | μm−1 s−1 | μm−1 s−1 | |
CMP | 2800 ± 400 | 0.043 ± 0.006 | 15 ± 3 | 0.38 ± 0.2 |
2′C-Me-CMP | 1600 ± 67 | 0.034 ± 0.002 | 20 ± 1 | 0.47 ± 0.2 |
2′C-Me-2′F-CMP | 2100 ± 100 | 0.024 ± 0.002 | 12 ± 1 | 0.92 ± 0.3 |
UMP | 0.05 ± 0.02 | |||
2′C-Me-2′F-UMP | ≤0.004 |