This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liu, S.-H.
Right arrow Articles by Cheng, Y.-C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, S.-H.
Right arrow Articles by Cheng, Y.-C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 1998, p. 833-839, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Unique Metabolism of a Novel Antiviral L-Nucleoside Analog, 2'-Fluoro-5-Methyl-beta -L-Arabinofuranosyluracil: a Substrate for Both Thymidine Kinase and Deoxycytidine Kinase

Shwu-Huey Liu, Kristie L. Grove, and Yung-Chi Cheng*

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

Received 12 September 1997/Returned for modification 5 November 1997/Accepted 13 January 1998

2'-Fluoro-5-methyl-beta -L-arabinofuranosyluracil (L-FMAU) is the first L-nucleoside analog with low cytotoxicity discovered to have potent antiviral activities against both hepatitis B virus and Epstein-Barr virus but not human immunodeficiency virus. This spectrum of activity is different from those of the other L-nucleoside analogs examined. L-FMAU enters cells through equilibrative-sensitive and -insensitive nucleoside transport as well as through nonfacilitated passive diffusion. L-FMAU is phosphorylated stepwise in cells to its mono-, di-, and triphosphate forms. In the present study the enzymes responsible for the first step of L-FMAU phosphorylation were identified. This is the first thymidine analog shown to be a substrate not only for cytosolic thymidine kinase and mitochondrial deoxypyrimidine kinase but also for deoxycytidine kinase. This finding suggests that the antiviral activity of L-FMAU will not be limited by the loss or alteration of any of these deoxynucleoside kinases.

* Corresponding author. Mailing address: Department of Pharmacology, Yale University School of Medicine, Sterling Hall of Medicine, 333 Cedar St., New Haven, CT 06510. Phone: (203) 785-7119. Fax: (203) 785-7129. E-mail: cheng.Lab{at}Yale.edu.

Antimicrobial Agents and Chemotherapy, April 1998, p. 833-839, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Krishnan, P., Gullen, E. A., Lam, W., Dutschman, G. E., Grill, S. P., Cheng, Y.-c. (2003). Novel Role of 3-Phosphoglycerate Kinase, a Glycolytic Enzyme, in the Activation of L-Nucleoside Analogs, a New Class of Anticancer and Antiviral Agents. J. Biol. Chem. 278: 36726-36732 [Abstract] [Full Text]  
  • Seigneres, B., Martin, P., Werle, B., Schorr, O., Jamard, C., Rimsky, L., Trepo, C., Zoulim, F. (2003). Effects of Pyrimidine and Purine Analog Combinations in the Duck Hepatitis B Virus Infection Model. Antimicrob. Agents Chemother. 47: 1842-1852 [Abstract] [Full Text]  
  • Abdelhamed, A. M., Kelley, C. M., Miller, T. G., Furman, P. A., Cable, E. E., Isom, H. C. (2003). Comparison of Anti-Hepatitis B Virus Activities of Lamivudine and Clevudine by a Quantitative Assay. Antimicrob. Agents Chemother. 47: 324-336 [Abstract] [Full Text]  
  • Krishnan, P., Fu, Q., Lam, W., Liou, J.-Y., Dutschman, G., Cheng, Y.-C. (2002). Phosphorylation of Pyrimidine Deoxynucleoside Analog Diphosphates. SELECTIVE PHOSPHORYLATION OF L-NUCLEOSIDE ANALOG DIPHOSPHATES BY 3-PHOSPHOGLYCERATE KINASE. J. Biol. Chem. 277: 5453-5459 [Abstract] [Full Text]  
  • Kira, T., Grill, S. P., Dutschman, G. E., Lin, J.-S., Qu, F., Choi, Y., Chu, C. K., Cheng, Y.-C. (2000). Anti-Epstein-Barr Virus (EBV) Activity of beta -L-5-Iododioxolane Uracil Is Dependent on EBV Thymidine Kinase. Antimicrob. Agents Chemother. 44: 3278-3284 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»