Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Aug;37(8):1720–1722. doi: 10.1128/aac.37.8.1720

The 5'-triphosphates of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolane-5-yl]cytosine equally inhibit human immunodeficiency virus type 1 reverse transcriptase.

J E Wilson 1, J L Martin 1, K Borroto-Esoda 1, S Hopkins 1, G Painter 1, D C Liotta 1, P A Furman 1
PMCID: PMC188052  PMID: 7692813

Abstract

The (-) enantiomer of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolane-5-yl]cytosine is a potent inhibitor of human immunodeficiency virus type 1 in vitro. The 5'-triphosphates of the (-) and (+) enantiomers equally inhibited the production of full-length minus-strand DNA in an endogenous reverse transcriptase reaction, each competitively inhibited DNA synthesis, and each was used as a chain-terminating substrate.

Full text

PDF
1722

Images in this article

1721Image
on p.1721
1722Image
on p.1722

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Coates J. A., Cammack N., Jenkinson H. J., Mutton I. M., Pearson B. A., Storer R., Cameron J. M., Penn C. R. The separated enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro. Antimicrob Agents Chemother. 1992 Jan;36(1):202–205. doi: 10.1128/aac.36.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Furman P. A., Davis M., Liotta D. C., Paff M., Frick L. W., Nelson D. J., Dornsife R. E., Wurster J. A., Wilson L. J., Fyfe J. A. The anti-hepatitis B virus activities, cytotoxicities, and anabolic profiles of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Antimicrob Agents Chemother. 1992 Dec;36(12):2686–2692. doi: 10.1128/aac.36.12.2686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hart G. J., Orr D. C., Penn C. R., Figueiredo H. T., Gray N. M., Boehme R. E., Cameron J. M. Effects of (-)-2'-deoxy-3'-thiacytidine (3TC) 5'-triphosphate on human immunodeficiency virus reverse transcriptase and mammalian DNA polymerases alpha, beta, and gamma. Antimicrob Agents Chemother. 1992 Aug;36(8):1688–1694. doi: 10.1128/aac.36.8.1688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Martin J. L., Wilson J. E., Furfine E. S., Hopkins S. E., Furman P. A. Biochemical analysis of human immunodeficiency virus-1 reverse transcriptase containing a mutation at position lysine 263. J Biol Chem. 1993 Feb 5;268(4):2565–2570. [PubMed] [Google Scholar]
  5. Miller W. H., Daluge S. M., Garvey E. P., Hopkins S., Reardon J. E., Boyd F. L., Miller R. L. Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity. J Biol Chem. 1992 Oct 15;267(29):21220–21224. [PubMed] [Google Scholar]
  6. Reardon J. E., Miller W. H. Human immunodeficiency virus reverse transcriptase. Substrate and inhibitor kinetics with thymidine 5'-triphosphate and 3'-azido-3'-deoxythymidine 5'-triphosphate. J Biol Chem. 1990 Nov 25;265(33):20302–20307. [PubMed] [Google Scholar]
  7. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Schinazi R. F., McMillan A., Cannon D., Mathis R., Lloyd R. M., Peck A., Sommadossi J. P., St Clair M., Wilson J., Furman P. A. Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Antimicrob Agents Chemother. 1992 Nov;36(11):2423–2431. doi: 10.1128/aac.36.11.2423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Soudeyns H., Yao X. I., Gao Q., Belleau B., Kraus J. L., Nguyen-Ba N., Spira B., Wainberg M. A. Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog. Antimicrob Agents Chemother. 1991 Jul;35(7):1386–1390. doi: 10.1128/aac.35.7.1386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. St Clair M. H., Richards C. A., Spector T., Weinhold K. J., Miller W. H., Langlois A. J., Furman P. A. 3'-Azido-3'-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase. Antimicrob Agents Chemother. 1987 Dec;31(12):1972–1977. doi: 10.1128/aac.31.12.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. White E. L., Parker W. B., Macy L. J., Shaddix S. C., McCaleb G., Secrist J. A., 3rd, Vince R., Shannon W. M. Comparison of the effect of Carbovir, AZT, and dideoxynucleoside triphosphates on the activity of human immunodeficiency virus reverse transcriptase and selected human polymerases. Biochem Biophys Res Commun. 1989 Jun 15;161(2):393–398. doi: 10.1016/0006-291x(89)92611-9. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES