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HEIDELBERG UNIVERSITY

Luise Krauth-Siegel 
Trypanosomes & Drug Design

Groupleader: Luise Krauth-Siegel

2012
Lizzi F, Veronesi G, Belluti F, Bergamini C, López-Sánchez A, Kaiser M, Brun R, Krauth-Siegel RL, Hall DG, Rivas L, Bolognesi ML. Conjugation of quinones with natural polyamines: toward an expanded antitrypanosomatid profile.
J Med Chem. 2012; 55(23):10490-500.

Eichhorn T, Schloissnig S, Hahn B, Wendler A, Mertens R, Lehmann WD, Krauth-Siegel RL, Efferth T. Bioinformatic and experimental fishing for artemisinin-interacting proteins from human nasopharyngeal cancer cells.
Mol Biosyst. 2012; 8(4):1311-8.

Krauth-Siegel RL, Leroux AE. Low-molecular-mass antioxidants in parasites.
Antioxid Redox Signal. 2012; 17(4):583-607.

Fueller F, Jehle B, Putzker K, Lewis JD, Krauth-Siegel RL. High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin.
J Biol Chem. 2012; 287(12):8792-802.

2011
Eberle, C., Lauber, B. S., Fankhausen, D., Kaiser, M., Brun, R., Krauth-Siegel, R. L. and Diederich, F. (2011) Improved inhibitors of trypanothione reductase by combination of motifs: Synthesis, inhibitory potency, binding mode, and antiprotozoal activities. Chem. Med. Chem. 6, 292-301.

Roldán, A., Comini, M. A., Crispo, M., and Krauth-Siegel, R. L. (2011) Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei. Mol. Microbiol. 81, 623-639.

Diechtierow, M. and Krauth-Siegel, R.L. (2011) A tryparedoxin-dependent peroxidase protects
African trypanosomes from membrane damage. Free Radic. Biol. Med. 51, 856-868.

2010
Ceylan S, Seidel V, Ziebart N, Berndt C, Dirdjaja N, Krauth-Siegel RL. The dithiol glutaredoxins of african trypanosomes have distinct roles and are closely linked to the unique trypanothione metabolism.
J Biol Chem. 2010; 285(45):35224-37.

Bakker BM, Krauth-Siegel RL, Clayton C, Matthews K, Girolami M, Westerhoff HV, Michels PA, Breitling R, Barrett MP. The silicon trypanosome.
Parasitology. 2010; 137(9):1333-41. Review.

Muhle-Goll C, Füller F, Ulrich AS, Krauth-Siegel RL. The conserved Cys76 plays a crucial role for the conformation of reduced glutathione peroxidase-type tryparedoxin peroxidase.
FEBS Lett. 2010; 584(5):1027-32.

2009
Eberle C, Burkhard JA, Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. Synthesis, inhibition potency, binding mode, and antiprotozoal activities of fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated diaryl sulfide scaffolds.
ChemMedChem. 2009; 4(12):2034-44.

Comini MA, Dirdjaja N, Kaschel M, Krauth-Siegel RL.Preparative enzymatic synthesis of trypanothione and trypanothione analogues.
Int J Parasitol. 2009; 39(10):1059-62.

Wenzel IN, Wong PE, Maes L, Müller TJ, Krauth-Siegel RL, Barrett MP, Davioud-Charvet E. Unsaturated Mannich bases active against multidrug-resistant Trypanosoma brucei brucei strains.
ChemMedChem. 2009; 4(3):339-51.

Stump B, Eberle C, Schweizer WB, Kaiser M, Brun R, Krauth-Siegel RL, Lentz D, Diederich F. Pentafluorosulfanyl as a novel building block for enzyme inhibitors: trypanothione reductase inhibition and antiprotozoal activities of diarylamines.
Chembiochem. 2009; 10(1):79-83.

Wendler A, Irsch T, Rabbani N, Thornalley PJ, Krauth-Siegel RL. Glyoxalase II does not support methylglyoxal detoxification but serves as a general trypanothione thioesterase in African trypanosomes.
Mol Biochem Parasitol. 2009; 163(1):19-27.

Ramos EI, Garza KM, Krauth-Siegel RL, Bader J, Martinez LE, Maldonado RA. 2,3-diphenyl-1,4-naphthoquinone: a potential chemotherapeutic agent against Trypanosoma cruzi.
J Parasitol. 2009; 95(2):461-6.

Cavalli A, Lizzi F, Bongarzone S, Brun R, Luise Krauth-Siegel R, Bolognesi ML.
Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase.
Bioorg Med Chem Lett. 2009; 19(11):3031-5.

Krauth-Siegel RL. Redox signaling and regulation in biology and medicine.
(editors: Jacob BC and Winyard PG), book review in
ChemMedChem. 2009; 4:2123-2127.

2008
Filser M, Comini MA, Molina-Navarro MM, Dirdjaja N, Herrero E, Krauth-Siegel RL. Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1.
Biol Chem. 2008; 389(1):21-32.

Krauth-Siegel RL, Comini MA. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism.
Biochim Biophys Acta. 2008; 1780(11):1236-48. Review.

Buchholz K, Comini MA, Wissenbach D, Schirmer RH, Krauth-Siegel RL, Gromer S. Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products.
Mol Biochem Parasitol. 2008; 160(1):65-9.

Melchers J, Krauth-Siegel RL, Muhle-Goll C. 1H, 13C, and 15N assignment of the oxidized and reduced forms of T. brucei glutathione peroxidase-type tryparedoxin peroxidase.
Biomolecular NMR Assignments. 2008; 2:65-68.

Comini MA, Rettig J, Dirdjaja N, Hanschmann EM, Berndt C, Krauth-Siegel RL. Monothiol glutaredoxin-1 is an essential iron-sulfur protein in the mitochondrion of African trypanosomes.
J Biol Chem. 2008; 283(41):27785-98.

Melchers J, Diechtierow M, Fehér K, Sinning I, Tews I, Krauth-Siegel RL, Muhle-Goll C. Structural basis for a distinct catalytic mechanism in Trypanosoma brucei tryparedoxin peroxidase.
J Biol Chem. 2008; 283(44):30401-11.

Beig M, Bender F, Oellien F, Rohwer A, Gaßel M, Selzer P, Unden G, Krauth-Siegel RL. Trypanothione reductase: a target protein for a combined in silico and in vitro screening approach.
Flavins and Flavoproteins 2008 (Frago S, Gómez-Moreno C, Medina M eds) Prensas Universitarias Zaragoza. 2008; 5503-8.

Stump B, Eberle C, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities.
Org Biomol Chem. 2008; 6(21):3935-47.

2007
Comini MA, Krauth-Siegel RL, Flohé L. Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes.
Biochem J. 2007, 402(1):43-9.

Melchers J, Dirdjaja N, Ruppert T, Krauth-Siegel RL. Glutathionylation of trypanosomal thiol redox proteins.
J Biol Chem. 2007, 282(12):8678-94.

Krauth-Siegel LR, Comini MA, Schlecker T. The trypanothione system.
Subcell Biochem. 2007, 44:231-51.

Schlecker T, Comini MA, Melchers J, Ruppert T, Krauth-Siegel RL. Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei.
Biochem J. 2007, 405(3):445-54.

Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. Betraying the Parasite's Redox System: Diaryl Sulfide-Based Inhibitors of Trypanothione Reductase: Subversive Substrates and Antitrypanosomal Properties.
ChemMedChem. 2007, 2(12):1708-1712.

2006
Otero L, Vieites M, Boiani L, Denicola A, Rigol C, Opazo L, Olea-Azar C, Maya JD, Morello A, Krauth-Siegel RL, Piro OE, Castellano E, González M, Gambino D, Cerecetto H. Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets.
J Med Chem. 2006, 49(11):3322-31.

2005
Lee B, Bauer H, Melchers J, Ruppert T, Rattray L, Yardley V, Davioud-Charvet E, Krauth-Siegel RL. Irreversible inactivation of trypanothione reductase by unsaturated mannich bases: a divinyl ketone as key intermediate.
J Med Chem. 2005, 48(23):7400-10.

Meiering S, Inhoff O, Mies J, Vincek A, Garcia G, Kramer B, Dormeyer M, Krauth-Siegel RL. Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis.
J Med Chem. 2005, 48(15):4793-802.

Werner C, Stubbs MT, Krauth-Siegel RL, Klebe G. The crystal structure of Plasmodium falciparum glutamate dehydrogenase, a putative target for novel antimalarial drugs.
J Mol Biol. 2005, 349(3):597-607.

Schlecker T, Schmidt A, Dirdjaja N, Voncken F, Clayton C, Krauth-Siegel RL. Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei.
J Biol Chem. 2005, 280(15):14385-94.

Krauth-Siegel RL, Bauer H, Schirmer RH. Dithiolproteine als Hüter des intrazellulären Redoxmilieus bei Parasiten: alte und neue Wirkstoff-Targets bei Trypanosomiasis und Malaria.
Angew Chem. 2005, 117:698-724.

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. 2005, 44(5):690-715.

Krauth-Siegel RL, Davioud-Charvet E. Trypanothione reductase and other flavoenzymes as targets of antiparasitic drugs.
Flavins and Flavoproteins 2005 (Nishino T, Miura R, Tanokura M, Fukui K Ed.)
ArchiTect Inc Tokyo. 2005, 867-76.

2004
Irsch T, Krauth-Siegel RL.Glyoxalase II of African trypanosomes is trypanothione-dependent.
J Biol Chem. 2004, 279(21):22209-17.

2003
Friemann R, Schmidt H, Ramaswamy S, Forstner M, Krauth-Siegel RL, Eklund H. Structure of thioredoxin from Trypanosoma brucei brucei.
FEBS Lett. 2003, 554:301-305.

Schmidt H, Krauth-Siegel RL. Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei.
J Biol Chem. 2003, 278(47): 46329-36.

Müller S, Liebau E, Walter RD, Krauth-Siegel RL. Thiol-based redox metabolism of protozoan parasites.
Trends Parasitol. 2003, 19(7):320-8.

Krauth-Siegel RL, Meiering SK, Schmidt H. The parasite-specific trypanothione metabolism of trypanosoma and leishmania.
Biol Chem. 2003, 384(4):539-49.

Krauth-Siegel RL, Inhoff O. Parasite-specific trypanothione reductase as a drug target molecule.
Parasitol Res. 2003, 90 Suppl 2: 77-85.

Gutierrez-Correa J, Krauth-Siegel RL, Stoppani AO. Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers.
Free Radic Res. 2003, 37(3):281-91.

2002
Werner C, Stubbs MT, Klebe G, Krauth-Siegel RL. The crystal structure of lipoamide dehydrogenase from Trypanosoma cruzi: A target for the design of new drugs against Chagas’ disease.
Flavins and Flavoproteins 2002, :917-922

Shahi SK, Krauth-Siegel RL, Clayton CE. Overexpression of the putative thiol conjugate transporter TbMRPA causes melarsoprol resistance in Trypanosoma brucei.
Mol Microbiol. 2002, 43(5):1129-38.

Breidbach T, Scory S, Krauth-Siegel RL, Steverding D. Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator deferoxamine.
Int J Parasitol. 2002, 32(4):473-9.

Krauth-Siegel RL, Schmidt H, Trypanothione and tryparedoxin in ribonucleotide reduction.
Methods Enzymol. 2002, 347:259-66.

Schmidt H., Schmidt A., Krauth-Siegel RL. Der parasitäre Trypanothion-Stoffwechsel-einzigartig und lebensnotwendig.
BIOforum. 2002, 7-8:478-480.

Schmidt A, Clayton C, Krauth-Siegel RL. Silencing of the thioredoxin gene in Trypanosoma brucei brucei.
Mol. Biochem. Parasitol. 2002, 125:207-210

Reckenfelderbäumer, N., Krauth-Siegel, R. L. Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. J. Biol. Chem. 2002, 277, 17548-17555.

Inhoff, O., Richards, J. M., Briet, J. W., Lowe, G., Krauth-Siegel, R. L. Coupling of a competitive and an irreversible ligand generates mixed type inhibitors of Trypanosoma cruzi trypanothione reductase. J. Med. Chem. 2002, 45, 4524-4530.

Schmidt, A., Krauth-Siegel, R. L. Enzymes of the trypanothione metabolism as targets for antitrypanosomal drug development. Current Topics Med. Chem. 2002, 2, 1239-1259.

2001
Dormeyer, M., Reckenfelderbäumer, N., Lüdemann, H., Krauth-Siegel, R. L. Trypanothione-dependent synthesis of deoxyribonucleotides by Trypanosoma brucei ribonucleotide reductase. J. Biol. Chem. 2001, 276, 10602-10606.
 

 
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