TABLE 2.
Pre-steady-state kinetic parameters determined for the incorporation of clinically approved NRTI-TPs and 3′-azido- ddATP and 3′-azido-ddGTP by WT HIV-1 RT
| dNTPa/NRTI-TP | kpol (s−1)b | Kd (μM)b | kpol/Kd (μM−1 s−1) | Selectivityc |
|---|---|---|---|---|
| dATP | 24.4 ± 3.9 | 3.2 ± 1.2 | 7.6 | |
| ddATP | 5.4 ± 2.3 | 5.3 ± 1.7 | 1.0 | 7.5 |
| TDF-DP | 6.2 ± 1.0 | 4.3 ± 1.0 | 1.4 | 5.3 |
| 3′-Azido-ddATP | 23.2 ± 0.5 | 2.3 ± 0.8 | 10.2 | 0.7 |
| dCTP | 1.2 ± 0.7 | 1.1 ± 0.4 | 1.1 | |
| ddCTP | 0.4 ± 0.1 | 2.7 ± 1.3 | 0.2 | 6.7 |
| 3TC-TP | 0.023 ± 0.004 | 0.37 ± 0.20 | 0.06 | 17.8 |
| dGTP | 7.5 ± 1.1 | 4.2 ± 1.4 | 1.8 | |
| CBV-TP | 0.6 ± 0.2 | 4.0 ± 1.8 | 0.16 | 11.2 |
| 3′-Azido-ddGTP | 4.8 ± 1.1 | 2.8 ± 0.9 | 1.7 | 1.1 |
| TTP | 9.2 ± 1.3 | 2.2 ± 0.8 | 4.2 | |
| d4T-TP | 4.3 ± 1.2 | 2.7 ± 1.1 | 1.6 | 2.6 |
| AZT-TP | 8.8 ± 0.2 | 2.0 ± 0.1 | 4.4 | 1.0 |
a
dNTP, deoxynucleoside triphosphate.
b
Data are derived from at least three independent experiments and are expressed as means ± standard deviations. kpol, turnover number; Kd, apparent dissociation constant.
c
Selectivity was determined as follows: (kpol/Kd)dNTP/(kpol/Kd)NRTI-TP.