Document Detail

Inhibitory effects of 5-alkyl- and 5-alkenyl-1-beta-D-arabinofuranosyluracil 5'-triphosphates on herpes virus-induced DNA polymerases.
MedLine Citation:
PMID:  2830244     Owner:  NLM     Status:  MEDLINE    
Various 5-substituted 1-beta-D-arabinofuranosyluracil 5'-triphosphates (H, methyl, ethyl, n-propyl, n-butyl, (E)-bromovinyl, styryl, and beta-phenylethyl derivatives) were prepared and their inhibitory effects on two different herpes virus-induced DNA polymerases (OMV and HCMV) were studied. These dTTP analogues inhibited the incorporation of [3H]dTMP into DNA in vitro. Among them, analogues having a vinyl group at the 5-position were strongly active against DNA polymerases induced on herpes virus infection. Kinetic analysis showed that the inhibition by the analogues was essentially competitive with respect to the substrate, dTTP. The K1 values (microM) for AraUTP (2.4), AraTTP (1.0), BVAUTP (0.8), and StUAUTP (0.8) were smaller than the Km value (microM) for dTTP (3.4), but those for AraEtUTP, AraPrUTP, and AraBuUTP (5-14) were larger than the Km for dTTP in the case of HCMV-induced DNA polymerase. In contrast to these results, OMV-induced DNA polymerase seemed to be more resistant to these inhibitors than HCMV-induced DNA polymerase. However, the mode of the structure of substituent groups at the 5-position of base moieties is almost the same for the two DNA polymerases, except for in the case of AraUTP itself.
S Suzuki; S Izuta; C Nakayama; M Saneyoshi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biochemistry     Volume:  102     ISSN:  0021-924X     ISO Abbreviation:  J. Biochem.     Publication Date:  1987 Oct 
Date Detail:
Created Date:  1988-03-25     Completed Date:  1988-03-25     Revised Date:  2007-12-19    
Medline Journal Info:
Nlm Unique ID:  0376600     Medline TA:  J Biochem     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  853-7     Citation Subset:  IM    
Faculty of Pharmaceutical Sciences, Hokkaido University.
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MeSH Terms
Antiviral Agents / pharmacology*
Arabinonucleotides / pharmacology*
Cytomegalovirus / enzymology
DNA-Directed DNA Polymerase / antagonists & inhibitors*
Herpesviridae / enzymology*,  physiology
Virus Replication / drug effects
Reg. No./Substance:
0/Antiviral Agents; 0/Arabinonucleotides; EC DNA Polymerase

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