TABLE 2.
Inhibition of HSV DNA polymerases by A-5021 triphosphatea
Polymerase | Km (μM)b dGTP |
Ki (μM) for indicated triphosphatec:
|
||
---|---|---|---|---|
A-5021 | ACV | (R,S)PCVd | ||
HSV-1 (KOS) | 0.24 ± 0.01 | 0.020 ± 0.002 | 0.0051 ± 0.0012 | 3.7 ± 0.1 |
HSV-2 (UW-268) | 0.18 ± 0.01 | 0.017 ± 0.003 | 0.0067 ± 0.0007 | 3.0 ± 0.2 |
Activated calf thymus DNA was used as the template primer. Values are the means ± standard errors of three determinations.
Km from Lineweaver-Burk plots.
Ki from secondary plots of Lineweaver-Burk plots.
All triphosphates of nucleoside analogs were chemically synthesized. (R,S)-PCV triphosphate was the racemic form, while the biosynthesized form in HSV-1-infected cells was almost entirely the (S)-enantiomer (>95%). In HSV-2-infected cells, 90% of the triphosphate was (S)- and 10% was the (R)-enantiomer (26).