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5 - Antitrypanosomal and Antileishmanial Targets

Published online by Cambridge University Press:  11 August 2009

Tag E. Mansour
With
Joan MacKinnon Mansour
Tag E. Mansour
Affiliation:
Stanford University, California
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Summary

The hemoflagellates of the genus Trypanosoma and of the genus Leishmania belong to the family of Trypanosomatidae. They are blood or tissue parasites that infect humans and other vertebrates. Trypanosoma brucei gambiense and T. brucei rhodesiense are the causative organisms of African trypanosomiasis (sleeping sickness), which is prevalent in central and eastern Africa. T. brucei can also infect all domestic animals. The vector of this disease is tsetse flies of the genus Glossina. Once the fly bites the mammalian host the metacyclic trypanosomes (mature stages in fly salivary glands) cause local skin “chancre” and then migrate to the lymphatic system of the host and eventually to the bloodstream. After approximately a month the parasites cross the choroid plexus into the brain and cerebrospinal fluid. The “sleeping” symptoms, such as physical depression, mental deterioration, and even coma, then appear in the host. The causative organism of American trypanosomiasis, also known as Chagas' disease, is Trypanosoma cruzi. It is present in South and Central America, especially in Brazil, Argentina, and Mexico. Vectors for transmission are members of Triatominae, insects found in Latin America. After having a blood meal from the human host the metacyclic forms of the trypanosome enter the gut of the insects and are eventually released in the insects' feces. When the feces are deposited on the skin of the host and rubbed they penetrate the skin and enter host cells where they are transformed to amastigotes, which cause chronic local inflammatory swelling.

Type
Chapter
Information
Chemotherapeutic Targets in Parasites
Contemporary Strategies
 , pp. 90 - 128
Publisher: Cambridge University Press
Print publication year: 2002

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References

Aronov, A. M., Suresh, S., Buckner, F. S., Voorhis, W. C., Verlinde, C. L., Opperdoes, F. R., Hol, W. G. & Gelb, M. H. (1999). Structure-based design of submicromolar, biologically active inhibitors of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase. Proc Natl Acad Sci USA, 96(8), 4273–4278CrossRefGoogle ScholarPubMed
Bacchi, C. J., Nathan, H. C., Hutner, S. H., McCann, P. P. & Sjoerdsma, A. (1980). Polyamine metabolism: A potential therapeutic target in trypanosomes. Science, 210(4467), 332–334CrossRefGoogle ScholarPubMed
Bacchi, C. J., Garofalo, J., Mockenhaupt, D., McCann, P. P., Diekema, K. A., Pegg, A. E., Nathan, H. C., Mullaney, E. A., Chunosoff, L., Sjoerdsma, A. & Hutner, S. H. (1983). In vivo effects of alpha-DL-difluoromethylornithine on the metabolism and morphology of Trypanosoma brucei brucei. Mol Biochem Parasitol, 7(3), 209–225CrossRefGoogle Scholar
Bakker, B. M., Westerhoff, H. V., Opperdoes, F. R. & Michels, P. A. (2000). Metabolic control analysis of glycolysis in trypanosomes as an approach to improve selectivity and effectiveness of drugs. Mol Biochem Parasitol, 106(1), 1–10CrossRefGoogle ScholarPubMed
Barrett, M. P., Tetaud, E., Seyfang, A., Bringaud, F. & Baltz, T. (1998). Trypanosome glucose transporters. Mol Biochem Parasitol, 91(1), 195–205CrossRefGoogle ScholarPubMed
Bart, G., Coombs, G. H. & Mottram, J. C. (1995). Isolation of lmcpc, a gene encoding a Leishmania mexicana cathepsin-B-like cysteine proteinase. Mol Biochem Parasitol, 73(1–2), 271–274CrossRefGoogle ScholarPubMed
Berens, R. L., Krug, E. C. & Marr, J. J. (1995). Purine and pyrimidine metabolism. In J. J. Marr & M. Muller (Eds.), Biochemistry and Molecular Biology of Parasites (pp. 89–118). San Diego: Academic PressCrossRef
Berman, J. D., Rainey, P. & Santi, D. V. (1983). Metabolism of formycin B by Leishmania amastigotes in vitro. Comparative metabolism in infected and uninfected human macrophages. J Exp Med, 158(1), 252–257CrossRefGoogle ScholarPubMed
Bitonti, A. J., Bacchi, C. J., McCann, P. P. & Sjoerdsma, A. (1985). Catalytic irreversible inhibition of Trypanosoma brucei brucei ornithine decarboxylase by substrate and product analogs and their effects on murine trypanosomiasis. Biochem Pharmacol, 34(10), 1773–1777CrossRefGoogle ScholarPubMed
Bond, C. S., Zhang, Y., Berriman, M., Cunningham, M. L., Fairlamb, A. H. & Hunter, W. N. (1999). Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure Fold Des, 7(1), 81–89CrossRefGoogle ScholarPubMed
Borst, P. & Fairlamb, A. H. (1998). Surface receptors and transporters of Trypanosoma brucei. Annu Rev Microbiol, 52, 745–778CrossRefGoogle ScholarPubMed
Bressi, J. C., Choe, J., Hough, M. T., Buckner, F. S., Voorhis, W. C., Verlinde, C. L., Hol, W. G. & Gelb, M. H. (2000). Adenosine analogues as inhibitors of Trypanosoma brucei phosphoglycerate kinase: Elucidation of a novel binding mode for a 2-amino-N(6)-substituted adenosine. J Med Chem, 43(22), 4135–4150CrossRefGoogle ScholarPubMed
Brohn, F. H. & Clarkson, A. B. Jr. (1980). Trypanosoma brucei brucei: Patterns of glycolysis at 37 degrees C in vitro. Mol Biochem Parasitol, 1(5), 291–305CrossRefGoogle ScholarPubMed
Buckner, F. S., Yokoyama, K., Nguyen, L., Grewal, A., Erdjument-Bromage, H., Tempst, P., Strickland, C. L., Xiao, L., Voorhis, W. C. & Gelb, M. H. (2000). Cloning, heterologous expression, and distinct substrate specificity of protein farnesyltransferase from Trypanosoma brucei. J Biol Chem, 275(29), 21870–21876CrossRefGoogle ScholarPubMed
Callahan, H. L. & Beverley, S. M. (1992). A member of the aldoketo reductase family confers methotrexate resistance in Leishmania. J Biol Chem, 267(34), 24165–24168Google ScholarPubMed
Carter, N. S. & Fairlamb, A. H. (1993). Arsenical-resistant trypanosomes lack an unusual adenosine transporter. Nature, 361(6408), 173–176. [Published erratum appears inNature 1993; 361(6410), 374.]CrossRefGoogle ScholarPubMed
Coombs, G. H. & Baxter, J. (1984). Inhibition of Leishmania amastigote growth by antipain and leupeptin. Ann Trop Med Parasitol, 78(1), 21–24CrossRefGoogle ScholarPubMed
Coombs, G. H. & Mottram, J. C. (1997). Parasite proteinases and amino acid metabolism: Possibilities for chemotherapeutic exploitation. Parasitology, 114(Suppl), S61–80Google ScholarPubMed
Cunningham, M. L. & Fairlamb, A. H. (1995). Trypanothione reductase from Leishmania donovani. Purification, characterisation and inhibition by trivalent antimonials. Eur J Biochem, 230(2), 460–468CrossRefGoogle ScholarPubMed
Docampo, R. (1990). Sensitivity of parasites to free radical damage by antiparasitic drugs. Chem Biol Interact, 73(1), 1–27CrossRefGoogle ScholarPubMed
Doering, T. L., Raper, J., Buxbaum, L. U., Adams, S. P., Gordon, J. I., Hart, G. W. & Englund, P. T. (1991). An analog of myristic acid with selective toxicity for African trypanosomes. Science, 252(5014), 1851–1854CrossRefGoogle ScholarPubMed
Doering, T. L., Lu, T., Werbovetz, K. A., Gokel, G. W., Hart, G. W., Gordon, J. I. & Englund, P. T. (1994). Toxicity of myristic acid analogs toward African trypanosomes. Proc Natl Acad Sci USA, 91(21), 9735–9739CrossRefGoogle ScholarPubMed
Donald, R. G. K., Carter, D., Ullman, B. & Roos, D. S. (1996). Insertional tagging, cloning, and expression of the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation. J Biol Chem, 271(24), 14010–14019CrossRefGoogle ScholarPubMed
Dumas, C., Ouellette, M., Tovar, J., Cunningham, M. L., Fairlamb, A. H., Tamar, S., Olivier, M. & Papadopoulou, B. (1997). Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J, 16(10), 2590–2598CrossRefGoogle ScholarPubMed
Eads, J. C., Scapin, G., Xu, Y., Grubmeyer, C. & Sacchettini, J. C. (1994). The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP. Cell, 78(2), 325–334CrossRefGoogle ScholarPubMed
Eakin, A. E., Mills, A. A., Harth, G., McKerrow, J. H. & Craik, C. S. (1992). The sequence, organization, and expression of the major cysteine protease (cruzain) from Trypanosoma cruzi. J Biol Chem, 267(11), 7411–7420Google ScholarPubMed
Eisenthal, R., Game, S. & Holman, G. D. (1989). Specificity and kinetics of hexose transport in Trypanosoma brucei. Biochim Biophys Acta, 985(1), 81–89CrossRefGoogle ScholarPubMed
el Kouni, M. H., Naguib, F. N., Panzica, R. P., Otter, B. A., Chu, S. H., Gosselin, G., Chu, C. K., Schinazi, R. F., Shealy, Y. F., Goudgaon, N., Ozerov, A. A., Ueda, T. & Iltzsch, M. H. (1996). Effects of modifications in the pentose moiety and conformational changes on the binding of nucleoside ligands to uridine phosphorylase from Toxoplasma gondii. Biochem Pharmacol, 51(12), 1687–1700CrossRefGoogle ScholarPubMed
Engel, J. C., Doyle, P. S., Hsieh, I. & McKerrow, J. H. (1998). Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med, 188(4), 725–734CrossRefGoogle ScholarPubMed
Englund, P., Ferguson, D., Guilbride, D., Johnson, C., Li, C., Perez-Morga, D., Rocco, L. & Torri, A. (1995). The replication of kinetoplast DNA. In J. Boothroyd & R. Komuniecki (Eds.), Molecular Approaches to Parasitology (Vol. 12, pp. 147–161). New York: Wiley-Liss
Fairlamb, A. (1982). Biochemistry of trypanosomiasis and rational approaches to chemotherapy. Trends Biochem Sci, 7, 249–253CrossRefGoogle Scholar
Fairlamb, A. H. & Bowman, I. B. (1980). Uptake of the trypanocidal drug suramin by bloodstream forms of Trypanosoma brucei and its effect on respiration and growth rate in vivo. Mol Biochem Parasitol, 1(6), 315–333CrossRefGoogle ScholarPubMed
Fairlamb, A. H. & Cerami, A. (1992). Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol, 46, 695–729CrossRefGoogle ScholarPubMed
Fairlamb, A. H., Henderson, G. B. & Cerami, A. (1989). Trypanothione is the primary target for arsenical drugs against African trypanosomes. Proc Natl Acad Sci USA, 86(8), 2607–2611CrossRefGoogle ScholarPubMed
Ferguson, M. A. & Cross, G. A. (1984). Myristylation of the membrane form of a Trypanosoma brucei variant surface glycoprotein. J Biol Chem, 259(5), 3011–3015Google ScholarPubMed
Focia, P. J., Craig, S. P. III, Nieves-Alicea, R., Fletterick, R. J. & Eakin, A. E. (1998). A 1.4 A crystal structure for the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi. Biochemistry, 37(43), 15066–15075CrossRefGoogle ScholarPubMed
Garforth, J., Yin, H., McKie, J. H., Douglas, K. T. & Fairlamb, A. H. (1997). Rational design of selective ligands for trypanothione reductase from Trypanosoma cruzi. Structural effects on the inhibition by dibenzazepines based on imipramine. J Enzyme Inhib, 12(3)161–173CrossRefGoogle ScholarPubMed
Goodwin, L. & Page, J. (1943). A study of the excretion of organic antimonials using a polarographic procedure. Biochem J, 37, 189–209CrossRefGoogle ScholarPubMed
Gourley, D. G., Luba, J., Hardy, L. W., Beverley, S. M. & Hunter, W. N. (1999). Crystallization of recombinant Leishmania major pteridine reductase 1 (PTR1). Acta Crystallogr D Biol Crystallogr, 55(Pt 9), 1608–1610CrossRefGoogle Scholar
Hardy, L. W., Matthews, W., Nare, B. & Beverley, S. M. (1997). Biochemical and genetic tests for inhibitors of Leishmania pteridine pathways. Exp Parasitol, 87(3)157–169CrossRefGoogle ScholarPubMed
Hofmann, B., Budde, H., Bruns, K., Guerrero, S. A., Kalisz, H. M., Menge, U., Montemartini, M., Nogoceke, E., Steinert, P., Wissing, J. B., Flohe, L. & Hecht, H. J. (2001). Structures of tryparedoxins revealing interaction with trypanothione. Biol Chem, 382(3), 459–471CrossRefGoogle ScholarPubMed
Hunter, W. N., Bailey, S., Habash, J., Harrop, S. J., Helliwell, J. R., Aboagye-Kwarteng, T., Smith, K. & Fairlamb, A. H. (1992). Active site of trypanothione reductase. A target for rational drug design. J Mol Biol, 227(1), 322–333CrossRefGoogle ScholarPubMed
Iltzsch, M. H. (1993). Pyrimidine salvage pathways in Toxoplasma gondii. J Eukaryot Microbiol, 40(1), 24–28CrossRefGoogle ScholarPubMed
Iltzsch, M. H., Uber, S. S., Tankersley, K. O. & el Kouni, M. H. (1995). Structure–activity relationship for the binding of nucleoside ligands to adenosine kinase from Toxoplasma gondii. Biochem Pharmacol, 49(10), 1501–1512CrossRefGoogle ScholarPubMed
Iten, M., Mett, H., Evans, A., Enyaru, J. C., Brun, R. & Kaminsky, R. (1997). Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to D, L-alpha-difluoromethylornithine. Antimicrob Agents Chemother, 41(9), 1922–1925Google ScholarPubMed
Jardim, A., Bergeson, S. E., Shih, S., Carter, N., Lucas, R. W., Merlin, G., Myler, P. J., Stuart, K. & Ullman, B. (1999). Xanthine phosphoribosyltransferase from Leishmania donovani. Molecular cloning, biochemical characterization, and genetic analysis. J Biol Chem, 274(48), 34403–34410CrossRefGoogle ScholarPubMed
Krieger, S., Schwarz, W., Ariyanayagam, M. R., Fairlamb, A. H., Krauth-Siegel, R. L. & Clayton, C. (2000). Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol Microbiol, 35(3), 542–552CrossRefGoogle ScholarPubMed
Krug, E. C., Marr, J. J. & Berens, R. L. (1989). Purine metabolism in Toxoplasma gondii. J Biol Chem, 264(18), 10601–10607Google ScholarPubMed
Kuntz, I., Meng, E. & Shoichet, B. (1994). Structure-based molecular design. Accounts Chem Res, 27, 117–123CrossRefGoogle Scholar
Kuntz, I. D. (1992). Structure-based strategies for drug design and discovery. Science, 257(5073), 1078–1082 [See comments.]CrossRefGoogle ScholarPubMed
Leonard, D. M. (1997). Ras farnesyltransferase: A new therapeutic target. J Med Chem, 40(19), 2971–2990CrossRefGoogle ScholarPubMed
Li, F., Hua, S. B., Wang, C. C. & Gottesdiener, K. M. (1996). Procyclic Trypanosoma brucei cell lines deficient in ornithine decarboxylase activity. Mol Biochem Parasitol, 78(1–2), 227–236CrossRefGoogle ScholarPubMed
Lima, A. P., Tessier, D. C., Thomas, D. Y., Scharfstein, J., Storer, A. C. & Vernet, T. (1994). Identification of new cysteine protease gene isoforms in Trypanosoma cruzi. Mol Biochem Parasitol, 67(2), 333–338CrossRefGoogle ScholarPubMed
Marr, J. J. (1991). Purine analogs as chemotherapeutic agents in leishmaniasis and American trypanosomiasis. J Lab Clin Med, 118(2), 111–119Google ScholarPubMed
Marr, J. J. & Ullman, B. (1995). Concepts of chemotherapy. In J. J. Marr & M. Muller (Eds.), Biochemistry and Molecular Biology of Parasites (pp. 323–336). San Diego: Academic PressCrossRef
Martinez, S. & Marr, J. J. (1992). Allopurinol in the treatment of American cutaneous leishmaniasis. N Engl J Med, 326(11), 741–744 [See comments.]CrossRefGoogle ScholarPubMed
McGrath, M. E., Eakin, A. E., Engel, J. C., McKerrow, J. H., Craik, C. S. & Fletterick, R. J. (1995). The crystal structure of cruzain: A therapeutic target for Chagas' disease. J Mol Biol, 247(2), 251–259CrossRefGoogle ScholarPubMed
McKerrow, J. H., Sun, E., Rosenthal, P. J. & Bouvier, J. (1993). The proteases and pathogenicity of parasitic protozoa. Annu Rev Microbiol, 47, 821–853CrossRefGoogle ScholarPubMed
Miles, R. W., Tyler, P. C., Evans, G. B., Furneaux, R. H., Parkin, D. W. & Schramm, V. L. (1999). Iminoribitol transition state analogue inhibitors of protozoan nucleoside hydrolases. Biochemistry, 38(40), 13147–13154CrossRefGoogle ScholarPubMed
Milord, F., Pepin, J., Loko, L., Ethier, L. & Mpia, B. (1992). Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sickness. Lancet, 340(8820), 652–655CrossRefGoogle ScholarPubMed
Morita, Y. S., Paul, K. S. & Englund, P. T. (2000). Specialized fatty acid synthesis in African trypanosomes: Myristate for GPI anchors. Science, 288(5463), 140–143CrossRefGoogle ScholarPubMed
Mottram, J. C., Robertson, C. D., Coombs, G. H. & Barry, J. D. (1992). A developmentally regulated cysteine proteinase gene of Leishmania mexicana. Mol Microbiol, 6(14), 1925–1932CrossRefGoogle ScholarPubMed
Nare, B., Luba, J., Hardy, L. W. & Beverley, S. (1997). New approaches to Leishmania chemotherapy: Pteridine reductase 1 (PTR1) as a target and modulator of antifolate sensitivity. Parasitology, 114(Suppl), S101–110Google ScholarPubMed
Nathan, H. C., Bacchi, C. J., Hutner, S. H., Rescigno, D., McCann, P. P. & Sjoerdsma, A. (1981). Antagonism by polyamines of the curative effects of alpha-difluoromethylornithine in Trypanosoma brucei brucei infections. Biochem Pharmacol, 30(21), 3010–3013CrossRefGoogle ScholarPubMed
Nelson, D. L. & Cox, M. M. (2000). Leninger Principles of Biochemistry (3rd ed.) pp. 845–847. New York: Worth
Ohkanda, J., Lockman, J. W., Yokoyama, K., Gelb, M. H., Croft, S. L., Kendrick, H., Harrell, M. I., Feagin, J. E., Blaskovich, M. A., Sebti, S. M. & Hamilton, A. D. (2001). Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity. Bioorg Med Chem Lett, 11(6), 761–764CrossRefGoogle ScholarPubMed
Paul, K., Jiang, D., Morita, Y. & Englund, P. (2001). Fatty acid synthesis in Aftican trypanosomes: A solution to the myristate mystery. Trends Parasitol, 17(8), 381–387CrossRefGoogle ScholarPubMed
Pelle, R., Schramm, V. L. & Parkin, D. W. (1998). Molecular cloning and expression of a purine-specific N-ribohydrolase from Trypanosoma brucei brucei. Sequence, expression, and molecular analysis. J Biol Chem, 273(4), 2118–2126CrossRefGoogle ScholarPubMed
Phillips, M. A., Coffino, P. & Wang, C. C. (1987). Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei. Implications for enzyme turnover and selective difluoromethylornithine inhibition. J Biol Chem, 262(18), 8721–8727Google ScholarPubMed
Plagemann, P. G., Wohlhueter, R. M. & Woffendin, C. (1988). Nucleoside and nucleobase transport in animal cells. Biochim Biophys Acta, 947(3), 405–443CrossRefGoogle ScholarPubMed
Poulin, R., Lu, L., Ackermann, B., Bey, P. & Pegg, A. E. (1992). Mechanism of the irreversible inactivation of mouse ornithine decarboxylase by alpha-difluoromethylornithine. Characterization of sequences at the inhibitor and coenzyme binding sites. J Biol Chem, 267(1), 150–158Google ScholarPubMed
Queen, S. A., Vander Jagt, D. & Reyes, P. (1988). Properties and substrate specificity of a purine phosphoribosyltransferase from the human malaria parasite, Plasmodium falciparum. Mol Biochem Parasitol, 30(2), 123–133CrossRefGoogle ScholarPubMed
Rainey, P. & Santi, D. V. (1983). Metabolism and mechanism of action of formycin B in Leishmania. Proc Natl Acad Sci USA, 80(1), 288–292CrossRefGoogle ScholarPubMed
Robello, C., Navarro, P., Castanys, S. & Gamarro, F. (1997). A pteridine reductase gene ptr1 contiguous to a P-glycoprotein confers resistance to antifolates in Trypanosoma cruzi. Mol Biochem Parasitol, 90(2), 525–535CrossRefGoogle ScholarPubMed
Rogers, S., Wells, R. & Rechsteiner, M. (1986). Amino acid sequences common to rapidly degraded proteins: The PEST hypothesis. Science, 234(4774), 364–368CrossRefGoogle ScholarPubMed
Rosenthal, P. J. (1999). Proteases of protozoan parasites. Adv Parasitol, 43, 105–159CrossRefGoogle ScholarPubMed
Sakanari, J. A., Nadler, S. A., Chan, V. J., Engel, J. C., Leptak, C. & Bouvier, J. (1997). Leishmania major: Comparison of the cathepsin L-and B-like cysteine protease genes with those of other trypanosomatids. Exp Parasitol, 85(1), 63–76CrossRefGoogle ScholarPubMed
Scheidt, K. A., Roush, W. R., McKerrow, J. H., Selzer, P. M., Hansell, E. & Rosenthal, P. J. (1998). Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg Med Chem, 6(12), 2477–2494CrossRefGoogle ScholarPubMed
Schwab, J. C., Afifi Afifi, M., Pizzorno, G., Handschumacher, R. E. & Joiner, K. A. (1995). Toxoplasma gondii tachyzoites possess an unusual plasma membrane adenosine transporter. Mol Biochem Parasitol, 70(1–2), 59–69CrossRefGoogle ScholarPubMed
Selzer, P. M., Chen, X., Chan, V. J., Cheng, M., Kenyon, G. L., Kuntz, I. D., Sakanari, J. A., Cohen, F. E. & McKerrow, J. H. (1997). Leishmania major: Molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors. Exp Parasitol, 87(3), 212–221CrossRefGoogle ScholarPubMed
Seyfang, A. & Duszenko, M. (1991). Specificity of glucose transport in Trypanosoma brucei. Effective inhibition by phloretin and cytochalasin B. Eur J Biochem, 202(1), 191–196CrossRefGoogle ScholarPubMed
Shapiro, T. A. (1994). Drugs affecting trypanosome topoisomerases. Adv Pharmacol, 29(B), 187–200CrossRefGoogle Scholar
Shapiro, T. A. & Englund, P. T. (1990). Selective cleavage of kinetoplast DNA minicircles promoted by antitrypanosomal drugs. Proc Natl Acad Sci USA, 87(3), 950–954CrossRefGoogle ScholarPubMed
Sjoerdsma, A. & Schechter, P. J. (1984). Chemotherapeutic implications of polyamine biosynthesis inhibition. Clin Pharmacol Ther, 35(3), 287–300CrossRefGoogle ScholarPubMed
Smith, K., Nadeau, K., Bradley, M., Walsh, C. & Fairlamb, A. H. (1992). Purification of glutathionylspermidine and trypanothione synthetases from Crithidia fasciculata. Protein Sci, 1(7), 874–883CrossRefGoogle ScholarPubMed
Smyth, J. D. (1994). Introduction to Animal Parasitology (3rd ed.), pp. 58–87. Cambridge: Cambridge University Press
Sullivan, W. J. Jr., Chiang, C. W., Wilson, C. M., Naguib, F. N., el Kouni, M. H., Donald, R. G. & Roos, D. S. (1999). Insertional tagging of at least two loci associated with resistance to adenine arabinoside in Toxoplasma gondii, and cloning of the adenosine kinase locus. Mol Biochem Parasitol, 103(1), 1–14CrossRefGoogle ScholarPubMed
Suresh, S., Bressi, J. C., Kennedy, K. J., Verlinde, C. L., Gelb, M. H. & Hol, W. G. (2001). Conformational changes in Leishmania mexicana glyceraldehyde-3-phosphate dehydrogenase induced by designed inhibitors. J Mol Biol, 309(2), 423–435CrossRefGoogle ScholarPubMed
Tabor, C. W. & Tabor, H. (1984). Polyamines. Annu Rev Biochem, 53, 749–790CrossRefGoogle ScholarPubMed
Tuttle, J. V. & Krenitsky, T. A. (1980). Purine phosphoribosyltransferases from Leishmania donovani. J Biol Chem, 255(3), 909–916Google ScholarPubMed
Ullman, B. & Carter, D. (1995). Hypoxanthine-guanine phosphoribosyltransferase as a therapeutic target in protozoal infections. Infect Agents Dis, 4(1), 29–40Google ScholarPubMed
Ullman, B. & Carter, D. (1997). Molecular and biochemical studies on the hypoxanthine-guanine phosphoribosyltransferases of the pathogenic haemoflagellates. nt J Parasitol, 27(2), 203–213CrossRefGoogle ScholarPubMed
Hellemond, J. J., Opperdoes, F. R. & Tielens, A. G. (1998). Trypanosomatidae produce acetate via a mitochondrial acetate:succinate CoA transferase. Proc Natl Acad Sci USA, 95(6), 3036–3041CrossRefGoogle Scholar
Visser, N., Opperdoes, F. R. & Borst, P. (1981). Subcellular compartmentation of glycolytic intermediates in Trypanosoma brucei. Eur J Biochem, 118(3), 521–526CrossRefGoogle ScholarPubMed
Waller, R. F., Keeling, P. J., Donald, R. G., Striepen, B., Handman, E., Lang-Unnasch, N., Cowman, A. F., Besra, G. S., Roos, D. S. & McFadden, G. I. (1998). Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proc Natl Acad Sci USA, 95(21), 12352–12357CrossRefGoogle ScholarPubMed
Wang, C. C. (1995). Molecular mechanisms and therapeutic approaches to the treatment of African trypanosomiasis. Annu Rev Pharmacol Toxicol, 35, 93–127CrossRefGoogle ScholarPubMed
Werbovetz, K. A., Bacchi, C. J. & Englund, P. T. (1996). Trypanocidal analogs of myristate and myristoyllysophosphatidylcholine. Mol Biochem Parasitol, 81(1), 115–118CrossRefGoogle ScholarPubMed
Wiemer, E. A., Michels, P. A. & Opperdoes, F. R. (1995). The inhibition of pyruvate transport across the plasma membrane of the bloodstream form of Trypanosoma brucei and its metabolic implications. Biochem J, 312(Pt 2), 479–484CrossRefGoogle ScholarPubMed
Wiemer, E. A., Kuile, B. H., Michels, P. A. & Opperdoes, F. R. (1992). Pyruvate transport across the plasma membrane of the bloodstream form of Trypanosoma brucei is mediated by a facilitated diffusion carrier. Biochem Biophys Res Commun, 184(2), 1028–1034CrossRefGoogle ScholarPubMed
Willson, M., Callens, M., Kuntz, D. A., Perie, J. & Opperdoes, F. R. (1993). Synthesis and activity of inhibitors highly specific for the glycolytic enzymes from Trypanosoma brucei. Mol Biochem Parasitol, 59(2), 201–210CrossRefGoogle ScholarPubMed
Yokoyama, K., Trobridge, P., Buckner, F. S., Scholten, J., Stuart, K. D., Voorhis, W. C. & Gelb, M. H. (1998a). The effects of protein farnesyltransferase inhibitors on trypanosomatids: Inhibition of protein farnesylation and cell growth. Mol Biochem Parasitol, 94(1), 87–97CrossRefGoogle Scholar
Yokoyama, K., Trobridge, P., Buckner, F. S., Voorhis, W. C., Stuart, K. D. & Gelb, M. H. (1998b). Protein farnesyltransferase from Trypanosoma brucei. A heterodimer of 61- and 65-kDa subunits as a new target for antiparasite therapeutics. J Biol Chem, 273(41), 26497–26505CrossRefGoogle Scholar
Zhang, Y., Bailey, S., Naismith, J. H., Bond, C. S., Habash, J., McLaughlin, P., Papiz, M. Z., Borges, A., Cunningham, M., Fairlamb, A. H.et al. (1993). Trypanosoma cruzi trypanothione reductase. Crystallization, unit cell dimensions and structure solution. J Mol Biol, 232(4), 1217–1220CrossRefGoogle ScholarPubMed
Zhang, Y., Bond, C. S., Bailey, S., Cunningham, M. L., Fairlamb, A. H. & Hunter, W. N. (1996). The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution. Protein Sci, 5(1), 52–61CrossRefGoogle ScholarPubMed

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