Abstract
Four acyclic guanosine analogs, the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, and acyclovir were compared in enzyme kinetic experiments, using purified herpes simplex virus type 2 thymidine kinase. All four analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by the viral thymidine kinase, but different affinities and relative rates of phosphorylation were observed.
Full text
PDF


Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- CLELAND W. W. The kinetics of enzyme-catalyzed reactions with two or more substrates or products. I. Nomenclature and rate equations. Biochim Biophys Acta. 1963 Jan 8;67:104–137. doi: 10.1016/0006-3002(63)91800-6. [DOI] [PubMed] [Google Scholar]
- Cheng Y. C., Ostrander M. Deoxythymidine kinase induced in HeLa TK- cells by herpes simplex virus type I and type II. II. Purification and characterization. J Biol Chem. 1976 May 10;251(9):2605–2610. [PubMed] [Google Scholar]
- De Clercq E. Antiviral and antitumor activities of 5-substituted 2'-deoxyuridines. Methods Find Exp Clin Pharmacol. 1980 Oct;2(5):253–267. [PubMed] [Google Scholar]
- Dobersen M. J., Greer S. An assay for pyrimidine deoxyribonucleoside kinase using gamma-32P-labeled ATP. Anal Biochem. 1975 Aug;67(2):602–610. doi: 10.1016/0003-2697(75)90335-8. [DOI] [PubMed] [Google Scholar]
- Elion G. B., Furman P. A., Fyfe J. A., de Miranda P., Beauchamp L., Schaeffer H. J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5716–5720. doi: 10.1073/pnas.74.12.5716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fyfe J. A., Keller P. M., Furman P. A., Miller R. L., Elion G. B. Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J Biol Chem. 1978 Dec 25;253(24):8721–8727. [PubMed] [Google Scholar]
- Keller P. M., Fyfe J. A., Beauchamp L., Lubbers C. M., Furman P. A., Schaeffer H. J., Elion G. B. Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activities. Biochem Pharmacol. 1981 Nov 15;30(22):3071–3077. doi: 10.1016/0006-2952(81)90495-0. [DOI] [PubMed] [Google Scholar]
- Larder B. A., Derse D., Cheng Y. C., Darby G. Properties of purified enzymes induced by pathogenic drug-resistant mutants of herpes simplex virus. Evidence for virus variants expressing normal DNA polymerase and altered thymidine kinase. J Biol Chem. 1983 Feb 10;258(3):2027–2033. [PubMed] [Google Scholar]
- Larsson A., Alenius S., Johansson N. G., Oberg B. Antiherpetic activity and mechanism of action of 9-(4-hydroxybutyl)guanine. Antiviral Res. 1983 Aug;3(2):77–86. doi: 10.1016/0166-3542(83)90028-1. [DOI] [PubMed] [Google Scholar]
- Larsson A., Oberg B., Alenius S., Hagberg C. E., Johansson N. G., Lindborg B., Stening G. 9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication. Antimicrob Agents Chemother. 1983 May;23(5):664–670. doi: 10.1128/aac.23.5.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith K. O., Galloway K. S., Kennell W. L., Ogilvie K. K., Radatus B. K. A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2. Antimicrob Agents Chemother. 1982 Jul;22(1):55–61. doi: 10.1128/aac.22.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
