Ribonucleotide reductase: target therapy for human disease

Bibliography

• KOLBERG M, STRAND KR, GRAFF Pet al.: Structure, function, and mechanism of ribonucleotide reductase. Biochemica Biophys Acta (2004) 1699:1–34.
   PubMed Web of Science ®Google Scholar
• ELLEDGE SJ, ZHOU Z, ALLEN JB: Ribonucleotide reductase: regulation, regulation, regulation. Trends Biochem. Sci. (1992) 17:119–123.
   PubMed Web of Science ®Google Scholar
• • Reviewed the importance of the enzyme to catalyse the rate-limiting step in converting ribonucleotide diphosphates to deoxynudeotide diphosphates.
   Google Scholar
• ELFORD HL, FREESE M, PASSAMIANI E et al.: Ribonucleotide reductase and cell proliferation. J. Biol. Chem. (1970) 245:5228–5233.
   PubMed Web of Science ®Google Scholar
• ELFORD HL: Functional regulation of mammalian ribonucleotide reductase. (1972) Adv. Enz. Reg. 10: 19–38.
   Google Scholar
• • Identified the relationship between the level of enzyme activity and the rate of cellular proliferation.
   Google Scholar
• WEBER G: Enzymology of cancer cells. N Engl. J. Med. (1977) 296:486–493.
   PubMed Web of Science ®Google Scholar
• STRYER L: Bioehemistrfi 5th Edition. Freeman 8c Company, NY, USA (2004).
   Google Scholar
• REICHARD P, EHRENBERG A: Ribonucleotide reductase - a radical enzyme. Science (1983) 221:514–519.
   PubMed Web of Science ®Google Scholar
• BJORKLUND S, SKOG S, TRIBUKAIT B et al.: S-phase-specific expression of mammalian ribonucleotide reductase R1 and R2 subunit mRNAs. Biochemistry (1990) 29:5452–5458.
   PubMed Web of Science ®Google Scholar
• REICHARD P: From RNA to DNA, why so many ribonucleotide reductases? Science (1993) 260:1773–1777.
   PubMedGoogle Scholar
• EKLUND H, UHLIN U, FARNEGARDH M et al.: Structure and function of the radical enzyme ribonucleotide reductase. Frog. Biophys. MoL BioL (2001) 77:177–268.
   PubMed Web of Science ®Google Scholar
• • Identified the three main groups ( classes) of the enzyme.
   Google Scholar
• FONTECAVE M, NORDLUND P, EKLUND H et al.: The redox centers of ribonucleotide reductase of Escherichia coli. Adv. EnqmoL (1992) 65:147–183.
   PubMedGoogle Scholar
• NORDLUND P, EKLUND H: Structure and function of the Escherichia coli ribonucleotide reductase protein R2. J. MoL Biol. (1993) 232:123–164.
   PubMed Web of Science ®Google Scholar
• THELANDER L, GRASLUND A: Ribonucleotide reductase in mammalian systems. In: Metal Ions in Biological Systems. Sigel HA (Ed.), Marcel-Dekker, Inc., NY, USA (1993) 30:109–129.
   Google Scholar
• • Confirmed the presence of the Class I RR subunit from murine tissues.
   Google Scholar
• LARSSON A, SJOBERG BM: Identification of the stable free radical tyrosine residue in ribonucleotide reductase. EMBO J. (1986) 5:2037–2040.
   PubMed Web of Science ®Google Scholar
• SAHLIN M, SJOBERG BM, BACKES G et al.: Activation of the iron-containing R2 protein of ribonucleotide reductase by hydrogen peroxide. Biochem. Biophys. Res. Commun. (1990) 167:813–818.
   PubMedGoogle Scholar
• HOLMGREN A: Thioredoxin and glutaredoxin systems. J. Biol. Chem. (1989) 264:13963–13966.
   PubMed Web of Science ®Google Scholar
• ELIASSON R, PONTIS E, JORDAN A et al.: Allosteric regulation of the third ribonucleotide reductase (NrdEF enzyme) from enterobacteriaceae. j Biol. Chem. (1996) 271:26582–26587.
   PubMedGoogle Scholar
• JORDON A, PONTIS E, ASLUND F et al.: The ribonucleotide reductase system of Lactocoecus lactis - characterization of an nrdEF enzyme and a new electron transport protein. J. Biol. Chem. (1996) 271:8779–8785.
   PubMedGoogle Scholar
• YANG FD, LU GZ, RUBIN H: Isolation of ribonucleotide reductase from Mycobacterium tuberculosis and cloning, expression, and purification of the large subunit. J BacterioL (1994) 176:6738–6743.
   PubMedGoogle Scholar
• SCOTTI C, VALBUZZI A, PEREGO M et al.: The Bacillus subtilis genes for ribonucleotide reductase are similar to the genes for the second class I NrdE/NrdF enzymes of Enterobacteriaceae. MicrobioL UK (1996) 142:2995–3004.
   PubMedGoogle Scholar
• FRASER CM, VENTER JC: The minimal gene complement of Myeoplasma genitalium. Science (1995) 270:397–403.
   PubMed Web of Science ®Google Scholar
• JORDAN A, GILBERT I, BARBE J: Two different operons for the same function: comparison of the Salmonella typhimurium nrdAb and nrclAF genes. Gene (1995) 167:75–79.
   PubMedGoogle Scholar
• JORDAN A. ARAGALL E, GILBERT I et al.: Promotor identification and expression analysis of Salmonella nphimurimum and Escherichia coli nrdEF operons encoding one of two class I ribonucleotide reductases present in both bacteria. MoL MicrobioL (1996) 19:777–790.
   Google Scholar
• BOOKERS, LIGHTS, BRODERICK Jet al.: Coenzyme B-12-dependent ribonucleotide reductase: evidence for the participation of five cysteine residues in ribonucleotide reaction. Biochemistry (1994) 33:12676–12685.
   Google Scholar
• STUBBE JA: Ribonucleotide reductases. Adv. EnzymoL (1990) 63:349–419.
   PubMedGoogle Scholar
• • Identified the presence of the obligatory radical produced by adenosylcobalamin.
   Google Scholar
• RIERA J, ROBB FT, WEISS R et al.: Ribonucleotide reductase in the archeon Pyrococcus furiosus: a critical enzyme in the evolution of the DNA genomes? Proc. Soc. Natl. Acad. Sci. USA (1997) 94:514–519.
   PubMedGoogle Scholar
• TAUER A, BENNER SA: The B-12 dependent ribonucleotide reductase in mammalian systems. In: Metal Ions in Biological Systems. Sigel, HA (Ed.), Marcel Dekker, Inc., NY, USA (1997) 30:109–129.
   Google Scholar
• UHLIN U, EKLUND H: The ten-stranded 0/a barrel in ribonucleotide reductase protein R1. J. MoL Biol. (1996) 262:358–369.
   PubMedGoogle Scholar
• ELIASSON R, FONTECAVE M, JORNVALL H et al.: The anaerobic ribonucleoside triphosphate reductase from Escherichia coli ribonucleotide reductase requires 5-adenosylmethionine as a cofactor. Proc. NatL Acad. Sci. USA (1990) 87:3314–3318.
   PubMedGoogle Scholar
• PADOVANI D, THOMAS F, TRAUTWEIN AX et al.: Activation of class III ribonucleotide reductase from Escherichia coli. The electron transfer from the iron-sulfur center to S-adenosylmethionine. Biochemistry (2001) 40:6713–6719.
   Google Scholar
• TORRENTS E, ELIASSON R, WOLPHNER H et al.: The anaerobic ribonucleotide reductase from Lactococcus lactis. Interactions between the two proteins NRDD and NRDG. J. Biol. Chem. (2001) 276:33488–33494.
   Google Scholar
• SUN XY, ELIAISSON R, PONTIS E et al.:Generation of the glycyl radical of the anaerobic Escherichia coli ribonucleotide reductase requires a specific activating enzyme. J. Biol. Chem. 270:2443-2446.
   Google Scholar
• MULLIEZ E, OLLAGNIER S, FONTECAVE M et al.: Formate is the hydrogen donor for the anaerobic ribonucleotide reductase from Escherichia coli. Proc. Natl. Acad. Soc. USA (1995) 92:8759–8762.
   PubMed Web of Science ®Google Scholar
• SUN X, OLLAGNIER S, SCHMIDT PP et al.: The free radical of the anaerobic ribonucleotide reductase from Escherichia coli is at glycine 681. J. Biol. Chem. (1996) 271:6827–6831.
   PubMed Web of Science ®Google Scholar
• ABERG A, NORLUND P, EKLUND H: Unusual clustering of carboxyl side chains in the core of iron-free ribonucleotide reductase. Nature (1993) 361:276–278.
   PubMed Web of Science ®Google Scholar
• LOGAN DT, DEMARE F, PERSSON BO et al.: Crystal structures of two self-hydroxylating ribonucleotide reductase protein R2 mutants: structural basis for the oxygen-insertion step of hydroxylation reactions catalyzed by diiron proteins. Biochemistry (1998) 37:10798–10807.
   PubMedGoogle Scholar
• EKBERG M, POTSCH S, SADIN E et al.:Preserved catalytic site in an engineered ribonucleotide reductase R2 protein with a nonphysiological radical transfer pathway. The importance of hydrogen bond connections between the participating residues. J. Biol. Chem. (1998) 273:21003–21008.
   Google Scholar
• GEREZ C, ELLEINGARD K, KAUPPI B et al.: Reactivity of the tyrosyl radical of Escherichia coli ribonucleotide reductase - control by the protein. Eur. J. Biochem. (1997) 249:401–407.
   PubMedGoogle Scholar
• LARSSON A, CLIMENT I, NORDLUND P et al.: Structural and functional characterization of two mutated R2 proteins of Escherichia coli ribonucleotide reductase. EMBO. J. (1996) 5:2037–2040.
   Google Scholar
• TONG W, BURDI D, RIGGS-GELASCO P et al.: Characterization ofY122F R2 of Escherichia coli ribonucleotide reductase by time-resolved physical biochemical methods and X-ray crystallography. Biochemistry (1998) 37:5840–5848.
   PubMedGoogle Scholar
• KAUPPI B, NIELSEN BA, RAMASWAMY S et al.: The three dimensional structure of mammalian ribonucleotide reductase protein R2 reveals a more-accessible iron-radical site then Escherichia coli. J. Mol. Biol. (1996) 262:706–720.
   PubMedGoogle Scholar
• ERIKSSON M, JORDAN A, EKLUND H: Structure of Salmonella iyphimurium nrdF ribonucleotide reductase in its oxidized and reduced form. Biochemistry (1998) 37:13359–13369.
   PubMedGoogle Scholar
• HUQUE Y: Radical generation and transfer in ribonucleotide reductase. Department of Molecular Biology and Functional Genomics, Stockholm University, Stockholm, Sweden (2001).
   Google Scholar
• UHLIN U, EKLUND H: Structure of ribonucleotide reductase protein Rl. Nature (1994) 370:533–539.
   PubMed Web of Science ®Google Scholar
• CARLSON J, FUCHS JA, MESSING J: Primary structure of the Escherichia coli ribonucleotide reductase operon. Proc. Natl Acad. Soc. USA (1984) 81:4294–4297.
   PubMedGoogle Scholar
• BOLLINGER JM JR, EDMONDSON DE, HUYNH BH et al.: Mechanism of assembly of the tyrosyl radical-dinuclear iron cluster cofactor of ribonucleotide reductase. Science (1991) 253:292–298.
   PubMedGoogle Scholar
• SAHLIN M, GRASLUND A, PETERSSON L et al.: Reduced forms of the iron-containing small subunit of ribonucleotide reductase from Escherichia coli. Biochemistry (1989) 28:2618–2625.
   PubMedGoogle Scholar
• SJOBERG BM, REICHARD P, GRASLUND A et al.: The tyrosine free radical in ribonucleotide reductase from Escherichia coli. j Biol. Chem. (1978) 253:6863–6865.
   PubMed Web of Science ®Google Scholar
• • Confirmed that the stability of the radical relies within the protein rather than being associated with the aromatic ring of the tyrosine residue.
   Google Scholar
• LOZANO G, ELLEDGE SJ: p53 sends nucleotides to repair DNA. Nature (2000) 404:24–25.
   PubMed Web of Science ®Google Scholar
• NAKANO K, BALINT E, ASHCROFT M et al.: A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene (2000) 19:4283–4289.
   PubMed Web of Science ®Google Scholar
• TANAKA H, ARAKAWA H, YAMAGUCHI T et al.: A ribonucleotide reductase gene involved in p53-dependent cell-cycle checkpoint for DNA damage. Nature (2000) 404:42–49.
   PubMed Web of Science ®Google Scholar
• CHABES A, THELANDER L: Controlledprotein degradation regulates ribonucleotide reductase activity in proliferating mammalian cells during the normal cell cycle and in response to DNA damage and replication blocks. J. Biol. Chem. (2000) 275:17747–17753.
   PubMedGoogle Scholar
• SANTOCANALE C, DIFFLEY JF: A Mecl- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. Nature (2000) 395:615–618.
   Google Scholar
• SZEKERES T, FRITZER-SZEKERES M, ELFORD HL: The enzyme ribonucleotide reductase: target for antitumor and anti-HIV therapy. Crit. Rev. Clin. Lab. Sci. (1997) 34:503–528.
   PubMed Web of Science ®Google Scholar
• • Showed that inhibtion of the RR enzyme inhibits cell proliferation.
   Google Scholar
• ELFORD HL: Effect of ribonucleotide reductase. Biochem. Biophys. Res. Commun. (1968) 33:129–135.
   PubMed Web of Science ®Google Scholar
• • Showed compounds like hydroxyurea inhibit the action of the RR enzyme.
   Google Scholar
• KRAKOFF IH: Clinical and pharmacological effects of hydroxyurea. In: Antineoplastic, and Immunosuppressive Agents. Part H. Sartorelli AC and Jones DG (Eds), Springer-Verlag, Berlin (1975):789–792.
   Google Scholar
• • Showed compounds like hydroxyurea inhibit the action of the RR enzyme.
   Google Scholar
• FONTECAVE M, ELIASSON R, REICHARD P: Enzymatic regulation of the radical content of the small subunit of Escherichia coli ribonucleotide reductase involving reduction of its redox centers. J. Biol Chem. (1989) 264:9164–9170.
   PubMedGoogle Scholar
• SAHLIN M, SJOBERG BM, BACKES G et al.: Activation of the iron-containing small subunit of ribonucleotide reductase from Escherichia coli. Biochemistry (1990) 28:2618–2625.
   Google Scholar
• DONEHOWER RC: An overview of the clinical experience with hydroxyurea. Semin. Oncol (1992) 19:11–19.
   PubMed Web of Science ®Google Scholar
• • Use of hydroxyurea for the treatment of chronic myelogeneous leukaemia.
   Google Scholar
• KENNEDY BJ: The evolution of hydroxyurea therapy in chronic myelogenous leukemia. Semin. Oncol (1992) 19:21–26.
   PubMedGoogle Scholar
• • Use of hydroxyurea for the treatment of chronic myelogeneous leukaemia.
   Google Scholar
• STEHMAN FB: Concurrent chemoradiation in carcinoma of the uterine cervix. Semin. Oncol (1992) 19:88–91.
   PubMedGoogle Scholar
• RANDI ML, RUZZON E, LUZZATTO G et al.: Safety profile of hydroxyurea in the treatment of patients with Philadelphia-negative chronic myeloproliferative disorders. Haematologica (2005) 90:261–262.
   PubMed Web of Science ®Google Scholar
• • Use of hydroxyurea for the treatment of polycythemia vera.
   Google Scholar
• FONTECAVE M: Ribonucleotide reductases and radical reactions. Cell Md. Sci. (1998) 54:684–695.
   PubMedGoogle Scholar
• • Inhibitors of the RR enzyme present in red wine, such as resveratrol, prevent heart disease.
   Google Scholar
• FINCH RA, LIU M, GRILL SP et al.: Triapine (3-aminopyridine-2-carboxaldehyde-thiosemicarbazone): a potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity. Biochem. Pharmacol (1992) 59:983–991.
   Google Scholar
• ELFORD HL, VAN'T RIET B: The inhibition of nucleoside diphosphates reductase by hydroxybenzodroxamic acid derivatives. In: Inhibitors of Ribonucleoside Diphosphate Reductase Activity. Cory JG, Cory AH (Eds), (1989):217–233.
   Google Scholar
• YOUNG CW, SCHOCHETMAN G, HODAS S et al: Inhibition of DNA synthesis by hydroxyurea: structure-activity relationships. Cancer Res. (1967) 27:535–540.
   PubMedGoogle Scholar
• • Showed that the carbonyl group within the hydroxamate moiety was the responsible unit to inhibit the RR enzyme.
   Google Scholar
• VAN'T RIET B, WAMPLER GL, ELFORD HL: Synthesis of hydroxy- and amino substituted benzohydroxamic acids: inhibition of ribonucleotide reductase and antitumor activity. J. Med. Chem. (1979) 22:589–592.
   PubMedGoogle Scholar
• • Showed generation of hydroxyl-substituted benzohydroxamic acids were more effective inhibitors of the RR enzyme when compared to hydroxyurea.
   Google Scholar
• ELFORD HL, WAMPLER GL, VAN'T REIT B: New ribonucleotide reductase inhibitors with antineoplastic activity. Cancer Res. (1979) 39:844–851.
   PubMed Web of Science ®Google Scholar
• • Demonstrated vicinyl polyhydroxyphenyl compounds possessed anticancer activity.
   Google Scholar
• ELFORD HL, VAN'T RIET B, WAMPLER GL et al.: Regulation of ribonucleotide reductase in mammalian cells by chemotherapeutic agents. Adv. Enz. Reg. (1981) 19:151–168.
   Google Scholar
• • Showed replenishing cells in vitro with fresh media restored cells to resume normal cell proliferation.
   Google Scholar
• ELFORD HL, ELFORD RM, WAMPLER GL et al.: New cancer chemotherapeutic agents that inhibit ribonucleotide reductase. In: New Approaches to the Design of Antineoplastic Agents. Bardos T, Kalman T (Eds), Elsevier Science, NY, USA (1982):151–168.
   Google Scholar
• • Showed vicinyl polyhydroxyphenyl compounds inhibit RR enzyme activity.
   Google Scholar
• BROWN NC, ELIASSON R, REICHARD P et al.: Spectrum and iron content of protein B2 from ribonucleotide diphosphates reductase. Eur. j Biochem. (1969) 9:512–518.
   PubMedGoogle Scholar
• ATKIN CL, THELANDER L, REICHARD P et al.: Iron and free radical in ribonucleotide reductase. Exchange of iron and Mossbauer spectroscopy of the protein B2 subunit of the Escherichia coli enqme. J. Biol. Chem. (1973) 248:7464–7472.
   Google Scholar
• PETERSSON L, GRASLUND A. EHRENBERG A et al.: The iron center in ribonucleotide reductase from Escherichia coli. J. Biol Chem. (1980) 225:6706–6712.
   Google Scholar
• VENKER P, HERZMANN H: Radikalangereigenschaften einiger Phenole. Naturewissenschafien (1960) 47:133–134.
   Google Scholar
• RAUKO P, ROMANOVA D, MIADOKOVA E al.: DNA-protective activity of new ribonucleotide reductase inhibitors. Anticancer Res. (1997) 17:3427–3440.
   Google Scholar
• KJOLLER-LARSEN I, SJOBERG BM, THELANDER L: Characterization of the active site of ribonucleotide reductase of Escherichia coli bacteriophage T4 and mammalian cells by inhibition studies with hydroxyurea analogues. Eur. J. Biochem. (1982) 125:75–81.
   PubMedGoogle Scholar
• STUBBE JA, ACKLES D: On the mechanism of ribonucleotide diphosphate reductase from Escherichia coli: Evidence for 3'-C-H bond cleavage. J. Biol Chem. (1980) 225:8027–8030.
   Google Scholar
• THELANDER L, GRASLUND A: Mechanism of inhibition of mammalian ribonucleotide reductase by the iron chelate ofl-formylisoquinoline thiosemicarbazone. J. Biol. Chem. (1983) 258:4063–4066.
   PubMed Web of Science ®Google Scholar
• CARMICHAEL J, CANTWELL BM, MANNIX KA: A Phase I and pharmacokinetic study of didox administered by 36-hr infusion. The Cancer Research Campaign Phase I/II Clinical Trials Committee. Br. J. Cancer (1990) 61:447–450.
   Google Scholar
• VEALE D, CARMICHAEL J, CANTWELL BM: A Phase I and pharmacokinetic study of didox: a ribonucleotide reductase inhibitor. Br. J. Cancer (1988) 58:70–72.
   PubMed Web of Science ®Google Scholar
• RUBENS RD, KAYE SB, SOUKOP M: Phase II trial of didox in advanced breast cancer. The Cancer Research Campaign Phase I/II Clinical Trials Committee. Br. J. Cancer (1991) 64:1187–1188.
   Google Scholar
• KRISTEN NL, RICCIO ES: The evaluation of didox in the Salmonella-Escherichia co/i/microsome plate incorporation assay. SRI International. Final Report, commissioned by the National Institute of Allergy and Infectious Disease (NIAID), NIH, Dr Charles Litterst, Program Officer. SRI International, 333 Ravenswood Ave, Menlo Park, CA (2002) report on file.
   Google Scholar
• INAYAT MS, CHENDIL D, MOHIUDDIN M et al.: Didox (a novel ribonucleotide reductase inhibitor) overcomes Bc1-2 mediated resistance in prostate cancer cell line, PC-3. Cancer Biol. Ther. (2002) 5:539–545.
   Google Scholar
• • Demonstrated the radiosensitisation effect of the vicinyl polyhydroxyphenyl compound didox, in p53 deficient/Bd-2 mediated resistant tumours of the prostate.
   Google Scholar
• BARRE-SINOUSI F, CHERMANN JC, REY F et al.: Isolation of a T-Iymphotrophic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science (1983) 220:868–871.
   PubMed Web of Science ®Google Scholar
• GOODENOW M, HUET T, SAURIN W et al.: HIV-1 isolates are rapidly evolving quasi-species: evidence for viral mixtures and preferred nucleotide substations. J. Acq. Imm. Defic. Syndr. (1989) 2:344–352.
   PubMedGoogle Scholar
• LIFSON JD, FEINBERG MB, REYES GR et al.: Induction of CD4 dependent cell fusion by the HTLV-III/LAV envelope glycoprotein. Nature (1986) 323:725–728.
   PubMed Web of Science ®Google Scholar
• SHAFER RW, WINTERS MA, PLAMER S et al.: Multiple concurrent reverse transcriptase and protease mutations and multidrug resistance of HIV-1 isolates from heavily treated patients. Ann. Inn. Med. (1988) 128:1515–1518.
   Google Scholar
• VIGOUROUX C, GHARAHANIAN S, SALHI Yet al.: Adverse metabolic disorders during highly active antiretroviral treatments (HAART) of HIV disease. Diabetes Metab. (1999) 25:383–393.
   Google Scholar
• DORNADULA G, ZHANG H, VAN ULTERT B et al.: Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. J. Am. Med. Assoc. (1999) 282:1627–1632.
   Google Scholar
• O'BRIEN WA, ZACH JA, CHEN IS: Molecular pathogenesis of HIV-1. AIDS (1990) 4:S41–S48.
   Google Scholar
• BALZARINI J: Effect of antimetabolite drugs of nucleotide metabolism on the anti-human immunodeficiency virus activity of nucleoside reverse transcriptase inhibitors. Pharmacol Ther. (2000) 87:175–187.
   PubMed Web of Science ®Google Scholar
• • Demonstrated that hydroxyurea reduced endogeneous dNTP levels within cells.
   Google Scholar
• BALARINI J, LEE CK, HERDEWIJIN P et al.: Mechanism of the potentiating effect of ribavirin on the activity of 2',3'-dideoxyinosine against human immunodeficiency virus. J. Biol. Chem. (1991) 266:21509–21514.
   PubMedGoogle Scholar
• JOHNS DG, GAO WY: Selective depletion of DNA precursors: an evolving strategy for potentiation of dideoxynucleoside activity against human immunodeficiency virus. Biochem. Pharmacol. (1998) 55:1551–1556.
   PubMed Web of Science ®Google Scholar
• LORI F, MALYKH A, CARA A et ell.: Hydroxyurea as an inhibitor of human immunodeficiency virus-type 1 replication. Science (1994) 266:801–805.
   Google Scholar
• • Showed interest in the clinical use of hydroxyurea for the treatment of HIV-infection.
   Google Scholar
• BIANCHI V, PONTIS E, REICHARD P: Changes of deoxyribonucleoside triphosphate pools induced by hydroxyurea and their relation to DNA synthesis. J. Biol Chem. (1986) 34:16037–16042.
   Google Scholar
• • Demonstrated that hydroxyurea depleted dNTP pools, espcially levels of dATP.
   Google Scholar
• SLABAUGH MB, HOWELL ML, WANG Y et al.: Deoxyadenosine reverses hydroxyurea inhibition of vaccine virus growth./ Virot (1991) 65:2290–2298.
   PubMedGoogle Scholar
• GAO WY JOHNS DG, CHOKEKUCHAI S et al.: Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2',3'-dideoxynucleoside activities against replication of human immunodeficiency virus. Proc. Natl. Acad. Sci. USA (1995) 92:8333–8337.
   Google Scholar
• GAO WY, MITSUYA H, DRISCOLL JS et al.: Enhancement by hydroxyurea of the anti-human immunodeficiency virus Type 1 potency of 2'43-fluoro-2',3'-dideoxyadenosine in peripheral blood mononuclear cells. Biochem. Pharmacol (1995) 50:274–276.
   PubMed Web of Science ®Google Scholar
• PALMER S, SHAFER RW, MERIGAN TC: Hydroxyurea enhances the activities of didanosine, 9-42-(phosphonylmethoxy)ethyll adenine, and 9- [2-(phosphonylmethoxy)propyl] adenine against drug-susceptible and drug-resistant human immunodeficiency virus isolates. Antimicrob. Agents Chemother. (1999) 43:2046–2050.
   PubMed Web of Science ®Google Scholar
• BIRON F, PONCEAU B, BOUHOUR D et al.: Long-term safety and antiretroviral activity of hydroxyurea and didanosine in HIV-patients. J. Acquir. Immune De*. Syndr. (2000) 25:329–336.
   PubMed Web of Science ®Google Scholar
• • Comparison of effects observed clinically with hydroxyurea and didanosine.
   Google Scholar
• RUTSCHMANN OT, OPRAVIL M, ITEN A et al.: Long-term hydroxyurea in combination with didanosine and stuvadine for the treatment of HIV-1 infection. Swiss Cohort Study. AIDS (2000) 14:2145–2151.
   Google Scholar
• • Comparison of effects observed clinically with hydroxyurea/didanosine/stavudine.
   Google Scholar
• LORI F: Hydroxyurea and HIV: 5 years later - from antiviral to immune-modulating effects. AIDS (1999) 13:1433–1442.
   PubMedGoogle Scholar
• • Comparison of effects observed clinically with hydroxyurea/didanosine/indinavir.
   Google Scholar
• MASERATI R: Hydroxyurea in the treatment of HIV-1 infection. J. Biol. Regul. Homest. Agents (1999) 13:181–185.
   PubMed Web of Science ®Google Scholar
• • Indicated that use of hydroxyurea for HD/ infection may be limited by its ability to induce myleosuppression.
   Google Scholar
• VILLANI P, MASERATI R, REGAZZI MB et al.: Pharmacokinetics of hydroxyurea in patients infected with human immunodeficiency virus Type I. J. Clin. PharmacoL (1996) 36:117–121.
   PubMed Web of Science ®Google Scholar
• LORI F, KELLY LM, FOLI A et ell.: Safety of hydroxyurea in the treatment of HIV infection. Expert Opin. Drug Saf (2004) 3:279–288.
   PubMedGoogle Scholar
• • Review of the clinical experience on the efficacy of hydroxyurea in the treatment of HIV infection.
   Google Scholar
• LORI F, POLLARD R, SHALIT P et al.: A low hydroxyurea (600 mg daily) is found optimal in a randomized, controlled trial (RIGHT 702) AIDS research and human retroviruses. in press.
   Google Scholar
• MURPHY R, KATLAMA C, AUTRAN B et al.: The effects of hydroxyurea or placebo combined with efavirenz, didanosine and stavudine in treatment naive and experienced patients: preliminary 24-week results from the 3D study. XIII International AIDS Conference, Durban, South Africa, WeOrB603 (2000).
   Google Scholar
• USSERY MA, KUNDER SC, GOLDERG G et al.: In vitro antiretroviral activity of ribonucleotide reductase inhibitors hydroxyurea, didox and trimidox in the HIV-infected HuPBMC SCID model and the Rauscher murine leukemia virus (RmuLV) model: mono-and combination therapy. In: Program. Abstract of the International Conference on AntimitocrobialAgents Chemotherapy. (1996) Abstract no. 112.
   Google Scholar
• • Demonstrated hydroxyl-susbstituted benzohydroxamic inhibitors are just as effective compared to hydroxyurea in the SCID-Hu and Rauscher viral leulmemic animal models, either as monotherapy or in combination therapy.
   Google Scholar
• MAYHEW CN, PHILLIPS JD, GREENBERG RN et al.: Effective use of ribonucleotide reductase inhibitors (didox and trimidox) alone or in combination with didanosine (ddI) to suppress disease progression and increase survival in murine acquired immunodeficiency syndrome (MAIDS). Cell. Mol Biol. (1999) 43:1019–1029.
   Google Scholar
• MAYHEW CN, MAMPURU LJ, CHENDIL D et al.: Suppression of retrovirus-induced immunodeficiency disease (murine AIDS) by trimidox and didox; novel ribonucleotide reductase inhibitors with less bone marrow toxicity than hydroxyurea. Anti vir. Res. (2002) 56:167–181.
   PubMedGoogle Scholar
• MAYHEW CN, PHILLIPS JD, GREENBERG RN et al.: In vivo and in vitro comparison of the short-term hematopoietic toxicity - hydroxyurea and trimidox or didox, novel ribonucleotide reductase inhibitors with potential HIV-1 activity. Stem Cells (1999) 17:1019–1029.
   Google Scholar
• SUMPTER LR, INAYAT MS, YOST EE et al.: In vivo examination of hydroxyurea and the novel ribonucleotide reductase inhibitors abacavir: suppression of retrovirus-induced immunodeficiency disease. Anti vir. Res. (2004) 62:111–120.
   PubMedGoogle Scholar
• MAYHEW CN, SUMPTER LN, INAYAT MS et al.: Combination of inhibitors of lymphocyte activation (hydroxyurea, trimidox, and didox) and reverse transcriptase (didanosine) suppresses development of murine retrovirus-induced lymphoproliferative disease. Anti vir. Res. (2005) 65:13–22.
   PubMedGoogle Scholar
• MAYHEW CN, PHILLIPS JD, CIBULL ML et al.: Short-term treatment with novel ribonucleotide reductase inhibitors Trimidox and Didox reverse late-stage murine retrovirus-induced lymphoproliferative disease with less bone marrow toxicity than hydroxyurea. Antivir. Chem. Chemother. (2002) 13:305–314.
   PubMedGoogle Scholar
• • Demonstrated hydroxyl-substituted benzohydroxamic acid inhibitors could reverse viral-induced altered pathologies when administered as late as 9 weeks post-viral infection in the MAIDS model of immunodeficiency disease.
   Google Scholar