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A comparison of the antiviral agents 2'-nor-2'-deoxyguanosine and acyclovir: uptake and phosphorylation in tissue culture and kinetics of in vitro inhibition of viral and cellular DNA polymerases by their respective triphosphates.

Abstract：

:A comparative study was conducted between the antiherpetic agents 2'-nor-2'-deoxyguanosine (2'NDG) and acyclovir (ACV) with respect to 1) the relative rates of uptake and phosphorylation to the "active" triphosphate species in tissue culture and 2) the in vitro inhibition of viral and cellular DNA polymerases by their respective triphosphates. The results indicated that a) six hours after HSV1 infection of primary rabbit kidney cells there was seven times more 2'NDG-triphosphate in the cells than ACV triphosphate; b) the relative rate of triphosphate formation in HSV1-infected versus uninfected cells was 4.5 times higher for 2'NDG than for ACV and c) the triphosphate of 2'NDG (2'NDG-TP) was a more selective inhibitor of the viral compared to the cellular DNA alpha-polymerase than the triphosphate of ACV (ACV-TP). The Km/Ki ratios for 2'NDG-TP and ACV-TP (in the competitive inhibition of dGTP) were 3.10 and 1.37, respectively, for the highly purified HSV1 polymerase; and 0.05 and 1.11, respectively, for the partially-purified HeLa alpha-polymerase. Neither triphosphate inhibited the HeLa DNA beta-polymerase to any significant extent. These results are in line with the findings [Ashton et al. (1982), Biochem. Biophys. Res. Commun. 108, 1716-1721] that 2'NDG has superior in vivo antiherpetic activity compared to ACV without apparent toxicity.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Germershausen J,Bostedor R,Field AK,Perry H,Liou R,Bull H,Tolman RL,Karkas JD

doi

10.1016/0006-291x(83)90530-2

subject

Has Abstract

pub_date

1983-10-31 00:00:00

pages

360-7

issue

2

eissn

0006-291X

issn

1090-2104

pii

0006-291X(83)90530-2

journal_volume

116

pub_type

杂志文章

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