Table 3.
Steady-state kinetic parameters for incorporation of the triphosphate forms of the 4′-substituted compounds by HIV-1 RT
| dNTP | Km (μM)a | kcat (min−1)a | kcat/Km (min−1 · μM−1) | Fold change in incorporation efficiencyb |
|---|---|---|---|---|
| dATP | 2.35 ± 0.06 | 0.66 ± 0.13 | 0.3 | 1 |
| EFdA-TP | 0.27 ± 0.01 | 3.47 ± 0.04 | 12.9 | 45.9 |
| EdDAP-TP | 0.15 ± 0.01 | 2.55 ± 0.10 | 17.0 | 60.7 |
| MedA-TP | 0.29 ± 0.01 | 1.24 ± 0.05 | 4.3 | 15.3 |
| EtdA-TP | 0.88 ± 0.19 | 3.41 ± 0.12 | 3.9 | 13.9 |
| dTTP | 0.60 ± 0.01 | 1.04 ± 0.12 | 1.7 | 1 |
| MedT-TP | 0.68 ± 0.22 | 1.58 ± 0.15 | 2.3 | 1.3 |
| EtdT-TP | 2.00 ± 0.22 | 1.44 ± 0.20 | 0.7 | 0.4 |
a
Values are means ± standard deviations of two independent experiments and were determined from the Michaelis-Menten equation using GraphPad Prism 4.
b
Fold change in incorporation efficiency is the ratio of the incorporation efficiency (kcat/Km) of NRTI-TP over that of dATP or dTTP [(kcat/Km)NRTI-TP/(kcat/Km)dATP or (kcat/Km)NRTI-TP/(kcat/Km)dTTP].