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Research Article

Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase

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Pages 784-794 | Received 01 Jun 2011, Accepted 07 Jul 2011, Published online: 15 Nov 2011

References

  • Kreier JP, Baker JR. Parasitic Protozoa. Winchester, MA: Allen & Unwin, 1987:43–89.
  • Fairlamb AH, Cerami A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol 1992;46:695–729.
  • Fairlamb AH, Blackburn P, Ulrich P, Chait BT, Cerami A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 1985;227:1485–1487.
  • Walsh C, Bradley M, Nadeau K. Molecular studies on trypanothione reductase, a target for antiparasitic drugs. Trends Biochem Sci 1991;16:305–309.
  • Krauth-Siegel RL, Comini MA. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim Biophys Acta 2008;1780:1236–1248.
  • Dumas C, Ouellette M, Tovar J et al. Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J 1997;16:2590–2598.
  • Tovar J, Wilkinson S, Mottram JC, Fairlamb AH. Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus. Mol Microbiol 1998;29:653–660.
  • Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, Krauth-Siegel RL, Clayton C. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol Microbiol 2000;35:542–552.
  • Austin SE, Khan MO, Douglas KT. Rational drug design using trypanothione reductase as a target for anti-trypanosomal and anti-leishmanial drug leads. Drug Des Discov 1999;16:5–23.
  • Krauth-Siegel RL, Inhoff O. Parasite-specific trypanothione reductase as a drug target molecule. Parasitol Res 2003;90 Suppl 2:S77–S85.
  • Krauth-Siegel RL, Bauer H, Schirmer RH. Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. Angew Chem Int Ed Engl 2005;44:690–715.
  • O’Sullivan MC. The battle against trypanosomiasis and leismaniasis: metal-based and natural product inhibitors of trypanothione reductase. Curr Med Chem – Anti-Infective Agents 2005;4:355–378.
  • Moreira DR, Leite AC, dos Santos RR, Soares MB. Approaches for the development of new anti-Trypanosoma cruzi agents. Curr Drug Targets 2009;10:212–231.
  • Garrard EA, Borman EC, Cook BN, Pike EJ, Alberg DG. Inhibition of trypanothione reductase by substrate analogues. Org Lett 2000;2:3639–3642.
  • Czechowicz JA, Wilhelm AK, Spalding MD, Larson AM, Engel LK, Alberg DG. The synthesis and inhibitory activity of dethiotrypanothione and analogues against trypanothione reductase. J Org Chem 2007;72:3689–3693.
  • el-Waer AF, Smith K, McKie JH, Benson T, Fairlamb AH, Douglas KT. The glutamyl binding site of trypanothione reductase from Crithidia fasciculata: enzyme kinetic properties of gamma-glutamyl-modified substrate analogues. Biochim Biophys Acta 1993;1203:93–98.
  • Tromelin A, Moutiez M, Meziane-Cherif D, Aumercier M, Tartar A, Sergheraert C. Synthesis of non reducible inhibitors for trypnothione reductase from Trypanosoma cruzi. Bioorg Med Chem Lett 1993;3:1971–1976.
  • Chan C, Yin H, Garforth J et al. Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. J Med Chem 1998;41:148–156.
  • Khan MO, Austin SE, Chan C et al. Use of an additional hydrophobic binding site, the Z site, in the rational drug design of a new class of stronger trypanothione reductase inhibitor, quaternary alkylammonium phenothiazines. J Med Chem 2000;43:3148–3156.
  • Leichus BN, Bradley M, Nadeau K, Walsh CT, Blanchard JS. Kinetic isotope effect analysis of the reaction catalyzed by Trypanosoma congolense trypanothione reductase. Biochemistry 1992;31:6414–6420.
  • Borges A, Cunningham ML, Tovar J, Fairlamb AH. Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase. Eur J Biochem 1995;228:745–752.
  • Still WC, Kahn M, Mitra A. Rapid chromatographic technique for preparative separations with moderate resolution. J Org Chem 1978;43:2923–2925.
  • Scholtz JM, Bartlett PA. A convenient differential protection strategy for functional group manipulation of aspartic and glutamic acids. Synthesis 1989:542–544.
  • Xaus N, Clapes P, Bardaji E, Torres JL, Jorba, X, Mata J, Valencia G. New enzymatic approach to the synthesis of convenient aspartic acid intermediates in peptide chemistry. Synthesis of N-benzyloxycarbonyl-l-aspartic acid β-allyl ester. Tetrahedron 1989;45:7421–7426.
  • Friedrich-Bochnitschek S, Waldmann H, Kunz H. Allyl esters as carboxy protecting groups in the synthesis of O-glycopeptides. J Org Chem 1989;54:751–756.
  • Li H, Jiang X, Ye YH, Fan C, Romoff T, Goodman M. 3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT): a new coupling reagent with remarkable resistance to racemization. Org Lett 1999;1:91–93.
  • Coste J, Le-Nguyen D, Castro B. PyBOP®: A new peptide coupling reagent devoid of toxic by-product. Tetrahedron Lett 1990;31:205–208.
  • Sullivan FX, Walsh CT. Cloning, sequencing, overproduction and purification of trypanothione reductase from Trypanosoma cruzi. Mol Biochem Parasitol 1991;44:145–147.
  • Sullivan FX, Shames SL, Walsh CT. Expression of Trypanosoma congolense trypanothione reductase in Escherichia coli: Overproduction, purification, and characterization. Biochemistry 1989;28:4986–4992.
  • el-Waer A, Douglas KT, Smith K, Fairlamb AH. Synthesis of N-benzyloxycarbonyl-L-cysteinylglycine 3-dimethylaminopropylamide disulfide: a cheap and convenient new assay for trypanothione reductase. Anal Biochem 1991;198:212–216.
  • Cleland WW. Statistical analysis of enzyme kinetic data. Methods Enzymol 1979;63:103–138.
  • Massey V, Williams CH Jr. On the reaction mechanism of yeast glutathione reductase. J Biol Chem 1965;240:4470–4480.
  • Bodanszky M. Principles of Peptide Synthesis, 2nd ed.; Berlin: Springer-Verlag, 1993:187–188
  • Ondetti MA, Deer A, Sheehan JT, Pluscec J, Kocy O. Side reactions in the synthesis of peptides containing the aspartyglycyl sequence. Biochemistry 1968;7:4069–4075.
  • Nuijens T, Cusan C, Kruijtzer JAW, Rijkers DTS, Liskamp RMJ, Quaedflieg PJLM. Versatile selective α-carboxylic acid esterification of N-protected amino acids and peptides by alcalase. Synthesis 2009:809–814.
  • For an earlier synthesis of a related derivative, see: Kremminger P, Undheim K. Asymmetric synthesis of unsaturated and bis-hydroxylated (S,S)- 2,7-diaminosuberic acid derivatives. Tetrahedron 1997;53:6925–6936.
  • Shames SL, Fairlamb AH, Cerami A, Walsh CT. Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases. Biochemistry 1986;25:3519–3526.
  • Krauth-Siegel RL, Enders B, Henderson GB, Fairlamb AH, Schirmer RH. Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. Eur J Biochem 1987;164:123–128.
  • Arscott DL, Thrope C, Williams CH Jr,. Glutathione reductase from yeast. Differential reactivity of the nascent thiols in two-electron reduced enzyme and properties of a monoalkylated derivative. Biochemistry 1981;20:1513–1520.
  • Jockers-Scherübl MC, Schirmer RH, Krauth-Siegel RL. Trypanothione reductase from Trypanosoma cruzi. Catalytic properties of the enzyme and inhibition studies with trypanocidal compounds. Eur J Biochem 1989;180:267–272.
  • Karplus PA, Krauth-Siegel RL, Schirmer RH, Schulz GE. Inhibition of human glutathione reductase by the nitrosourea drugs 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea. A crystallographic analysis. Eur J Biochem 1988;171:193–198.
  • Gallwitz H, Bonse S, Martinez-Cruz A, Schlichting I, Schumacher K, Krauth-Siegel RL. Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: crystallographic, kinetic, and spectroscopic studies. J Med Chem 1999;42:364–372.
  • Bond CS, Zhang Y, Berriman M, Cunningham ML, Fairlamb AH, Hunter WN. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 1999;7:81–89.
  • Lee B, Bauer H, Melchers J et al. Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J Med Chem 2005;48:7400–7410.

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