Partial selective inhibition of HIV-1 reverse transcriptase and human DNA polymerases γ and β by thiated 3'-fluorothymidine analogue 5'-triphosphates

Antiviral Research

Volumn 88, Issue 2, 2010, Pages 176-181

  Wińska, Patrycja ^a   Miazga, Agnieszka ^a   Poznański, Jarosław ^a   Kulikowski, Tadeusz ^a  

^a INSTITUTE OF BIOCHEMISTRY AND BIOPHYSICS   (Poland)

Author keywords

Antiretroviral agents; Human DNA polymerase; Nucleoside HIV 1 reverse transcriptase inhibitors

Indexed keywords

3' DEOXY 3' FLUORO 2 THIOTHYMIDINE 5' TRIPHOSPHATE; 3' DEOXY 3' FLUORO 4 THIOTHYMIDINE 5' TRIPHOSPHATE; 3' DEOXY 3' FLUOROTHYMIDINE 5' TRIPHOSHATE; 3' FLUOROTHYMIDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DNA DIRECTED DNA POLYMERASE BETA; DNA DIRECTED DNA POLYMERASE GAMMA; MITOCHONDRIAL ENZYME; RECOMBINANT ENZYME; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; THYMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DNA SYNTHESIS; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SELECTIVITY; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION;

ANTI-HIV AGENTS; DIDEOXYNUCLEOSIDES; DIDEOXYNUCLEOTIDES; DNA POLYMERASE BETA; DNA-DIRECTED DNA POLYMERASE; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MAGNETIC RESONANCE IMAGING; MOLECULAR CONFORMATION; POLYRIBONUCLEOTIDES; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; THYMINE NUCLEOTIDES;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77958150380     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2010.08.011     Document Type: Article

References (41)

1. Balzarini J., Baba M., Pauwels R., Herdewijn P., De Clerq E. Anti-retrovirus activity of 3'-fluoro- and 3'-azido-substituted pyrimidine 2',3'-dideoxynucleoside analogues. Biochem. Pharmacol. 1988, 37:2847-2856.
2. Balzarini J., Van Aerschot A., Pauwels R., Baba M., Schols D., Herdewijn P., De Clercq E. Halogeno-3'-fluoro-2',3'-dideoxyuridines as inhibitors of human immunodeficiency virus (HIV): potent and selective anti-HIV activity of 3'-fluoro-2',3'-dideoxy-5-chlorouridine. Mol. Pharmacol. 1989, 35:571-577.
3. Becher F., Pruvost A.G., Schlemmer D.D., Creminon C.A., Goujard C.M., Delfraissy J.F., Benech H.C., Grassi J.J. Significant levels of intracellular stavudine triphosphate are found in HIV-infected zidovudine-treated patients. AIDS 2003, 17:555-561.
4. Bienstock R.J., Copeland W.C. Molecular insights into NRTI inhibition and mitochondrial toxicity revealed from a structural model of the human mitochondrial DNA polymerase. Mitochondrion 2004, 4:203-213.
5. Cheng Y., Dutschman G.E., Bastow K.F., Sarngadharan M.G., Ting R.Y.C. Human immunodeficiency virus reverse transcriptase. General properties and its interactions with nucleoside triphosphate analogs. J. Biol. Chem. 1987, 262:2187-2189.
6. Cheng Y., Prusoff W.H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22:3099-3108.
7. Copeland W.C., Chen M.S., Wang T.S.-F. Human DNA polymerases alpha and beta are able to incorporate anti-HIV deoxynucleotides into DNA. J. Biol. Chem. 1992, 267:21459-21464.
8. Eriksson S., Xu B., Clayton D.A. Efficient incorporation of anti-HIV deoxynucleotides by recombinant yeast mitochondrial DNA polymerase. J. Biol. Chem. 1995, 270:18929-18934.
9. Faraj A., El Alaoui A.M., Gosselin G., Imbach J.L., Morrow C., Sommadossi J.P. Effects of beta-L-3'-azido-3'-deoxythymidine 5'-triphosphate on host and viral DNA polymerases. Antiviral Res. 2000, 47:97-102.
10. Focher F., Maga G., Bendiscioli A., Capobianco M., Colonna F., Garbesi A., Spadari S. Stereospecificity of human DNA polymerases alpha, beta, gamma, delta and epsilon, HIV-reverse transcriptase, HSV-1 DNA polymerase, calf thymus terminal transferase and Escherichia coli DNA polymerase I in recognizing d- and l-thymidine 5'-triphosphate as substrate. Nucleic Acids Res. 1995, 23:2840-2847.
11. Graves S.W., Johnson A.A., Johnson K.A. Expression, purification, and initial kinetic characterization of the large subunit of the human mitochondrial DNA polymerase. Biochemistry 1998, 37:6050-6058.
12. Hanes J.W., Johnson K.A. Exonuclease removal of dideoxycytidine (zalcitabine) by the human mitochondrial DNA polymerase. Antimicrob. Agents Chemother. 2008, 52:253-258.
13. 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, 36:1688-1694.
14. Huang P., Farquhar D., Plunkett W. Selective action of 2',3'-didehydro-2',3'-dideoxythymidine triphosphate on human immunodeficiency virus reverse transcriptase and human DNA polymerases. J. Biol. Chem. 1992, 267:2817-2822.
15. Johnson A.A., Ray A.S., Hanes J., Suo Z., Colacino J.M., Anderson K.S., Johnson K.A. Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase. J. Biol. Chem. 2001, 276:40847-40857.
16. Kaguni L.S. DNA polymerase gamma, the mitochondrial replicase. Annu. Rev. Biochem. 2004, 73:293-320.
17. Kakuda N.T. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin. Ther. 2000, 22:685-708.
18. König H., Behr E., Lower J., Kurth R. Azidothymidine triphosphate is an inhibitor of both human immunodeficiency virus Type 1 reverse transcriptase and DNA polymerase gamma. Antimicrob. Agents Chem. 1989, 33:2109-2114.
19. Lee H., Hanes J., Johnson K.A. Toxicity of nucleoside analogues used to treat AIDS and the selectivity of the mitochondrial DNA polymerase. Biochemistry 2003, 42:14711-14719.
20. Lewis W., Simpson J.F., Meyer R.R. Cardiac mitochondrial DNA polymerase-gamma is inhibited competitively and noncompetitively by phosphorylated zidovudine. Circ. Res. 1994, 74:344-348.
21. Lim S.E., Copeland W.C. Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase gamma. J. Biol. Chem. 2001, 276:23616-23623.
22. Longley M.J., Ropp P.A., Lim S.E., Copeland W.C. Characterization of the native and recombinant catalytic subunit of human DNA polymerase γ: identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity. Biochemistry 1998, 37:10529-10539.
23. Lund K.C., Peterson L.L., Wallace K.B. Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs. Antimicrob. Agents Chemother. 2007, 51:2531-2539.
24. Lund K.C., Wallace K.B. Direct, DNA pol-gamma-independent effects of nucleoside reverse transcriptase inhibitors on mitochondrial bioenergetics. Cardiovasc. Toxicol. 2004, 4:217-228.
25. Majumdar C., Abhotts J., Broder S., Wilson S.H. Studies on the mechanism of human immunodeficiency virus reverse transcriptase, steady-state kinetics, processivity, and polynucleotide inhibition. J. Biol. Chem. 1988, 263:15657-15665.
26. Martin J.L., Brown C.E., Matthews-Davis N., Reardon J.E. Effects of antiviral nucleoside analogs on human DNA polymerases and mitochondrial DNA synthesis. Antimicrob. Agents Chemother. 1994, 38:2743-2749.
27. Matthes E., Langen P., von Janta-Lipinski M., Will H., Schröder H.C., Mery H., Weiler B.E., Müller W.E.G. Potent inhibition of hepatitis B virus production in vitro by modified pyrimidine nucleosides. Antimicrob. Agents Chemother. 1990, 34:1986-1990.
28. Matthes E., Lehmann C., Scholz D., von Janta-Lipinski M., Gaertner K., Rosenthal H.A., Langen P. Inhibition of HIV-associated reverse transcriptase by sugar-modified derivatives of thymidine 5'-triphosphate in comparison to cellular DNA polymerases alpha and beta. Biochem. Biophys. Res. Commun. 1987, 148:78-85.
29. Matthes E., Lehmann C., von Janta-Lipinski M., Scholz D. Inhibition of HIV-replication by 3'-fluoro-modified nucleosides with low cytotoxicity. Biochem. Biophys. Res. Commun. 1989, 165:488-495.
30. Miazga A., Felczak K., Bretner M., Siwecka M.A., Piasek A., Kulikowski T. Thiated analogues of 2',3'-dideoxy-3'-fluorothymidine and their phosphorylated and phosphonylated derivatives: synthesis, interaction with HIV reverse transcriptase, and in vitro anti-HIV activity. Nucleosides Nucleotides Nucleic Acids 2003, 22:973-976.
31. Parker W.B., White E.L., Shaddix S.C., Ross L.J., Buckheit R.W., Germany J.M., Secrist J.A., Vince R., Shannon W.M. Mechanism of inhibition of human immunodeficiency virus type 1 reverse transcriptase and human DNA polymerases alpha, beta, and gamma by the 5'-triphosphates of carbovir, 3'-azido-3'-deoxythymidine, 2',3'-dideoxyguanosine, and 3'-deoxyguanosine. J. Biol. Chem. 1991, 266:1754-1762.
32. Poopeiko N.E., Poznański J., Drabikowska A., Balzarini J., De Clercq E., Mikhailopulo I.A., Shugar D., Kulikowski T. Synthesis, solution conformation and biological properties of 2',3'-dideoxy-3'-fluoro-d-erythro-pentofuranosides of 2-thiouracil and 2-thiothymidine. Nucleosides Nucleotides 1995, 14:435-437.
33. Poznański J., Felczak K., Kulikowski T., Remin M. 1H NMR conformational study of antiherpetic C5-substituted 2'-deoxyuridines: insight into the nature of structure-activity relationships. Biochem. Biophys. Res. Commun. 2000, 272:64-74.
34. 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, 265:20302-20307.
35. Remin M. A code relating sequence to structure in nucleic acids. Nucleosides Nucleotides Nucleic Acids 2001, 20:841-846.
36. Stahle L., Guzenda E., Ljungdahl-Stahle E. Pharmacokinetics and extracellular distribution to blood, brain, and muscle of alovudine (3'-fluorothymidine) and zidovudine in the rat studied by microdialysis. J. Acquir. Immune Defic. Syndr. 1993, 6:435-439.
37. Steet R.A., Melancon P., Kuchta R.D. 3'-Azidothymidine potently inhibits the biosynthesis of highly branched N-linked oligosaccharides and poly-N-acetyllactosamine chains in cells. J. Biol. Chem. 2000, 275:26812-26820.
38. Sundseth R., Joyner S.S., Moore J.T., Dornsife R.E., Dev I.K. The anti-human immunodeficiency virus agent 3'-fluorothymidine induces DNA damage and apoptosis in human lymphoblastoid cells. Antimicrob. Agents Chemother 1996, 40:331-335.
39. von Janta-Lipinski M., Costisella B., Ochs H., Hübscher U., Hafkemeyer P., Matthes E. Newly synthesized l-enantiomers of 3'-fluoro-modified beta-2'-deoxyribonucleoside 5'-triphosphates inhibit hepatitis B DNA polymerases but not the five cellular DNA polymerases alpha, beta, gamma, delta, and epsilon nor HIV-1 reverse transcriptase. J. Med. Chem. 1998, 41:2040-2046.
40. Vrang L., Bazin H., Remaud G., Chattopadhyaya J., Öberg B. Inhibition of the reverse transcriptase from HIV by 3'-azido-3'-deoxythymidine triphosphate and its threo analogue. Antiviral Res. 1987, 7:139-149.
41. Yang G., Dutschman G.E., Wang C.J., Tanaka H., Baba M., Anderson K.S., Cheng Y.C. Highly selective action of triphosphate metabolite of 4'-ethynyl D4T: a novel anti-HIV compound against HIV-1 RT. Antiviral Res. 2007, 73:185-191.