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Groupleader: Luise Krauth-Siegel
Luise Krauth-Siegel
Trypanosomes & Drug Design
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Research
Trypanosomes and leishmania, the causative agents of African sleeping sickness (Trypanosoma brucei), South American Chagas' disease (T. cruzi) and the different forms of leishmaniasis, have an unprecedented thiol redox metabolism. All of these parasitic protozoa lack glutathione reductase and thioredoxin reductases. The main non-protein thiols are glutathionylspermidine conjugates such as trypanothione [bis(glutathionyl)spermidine] which are kept reduced by the essential flavoenzyme trypanothione reductase.
Our work focuses on irreversible inhibitors and subversive substrates of trypanothione reductase as potential drug candidates. A second approach deals with the detoxification of hydroperoxides. African trypanosomes have 2-Cys-peroxiredoxins and glutathione peroxidase-type enzymes which both obtain their reducing equivalents from the unique cascade composed of trypanothione reductase, trypanothione and tryparedoxin. Site directed mutagenesis and the recent structural analysis revealed that the catalytic mechanism of the parasite glutathione peroxidase-type enzyme differs totally from that of the homologous mammalian selenoenzymes. The role of mono- and dithiol glutaredoxins in the redox metabolism of African trypanosomes is the third current focus.
Aim of our work is to elucidate the unique trypanothione metabolism of trypanosomatids and to contribute to the rational development of new antiparasitic drugs on the basis of specific enzyme inhibitors.
Download BZH Report Krauth-Siegel 2014-2016
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Academic Training and Positions
| 1982 | PhD from the Max-Planck-Institute for Medical Research Heidelberg |
| 1982-1995 | Staff member at the Institute of Biochemistry II of Heidelberg University |
| 1989 | Habilitation in Biochemistry |
| 1995-2003 | Apl. Professor for Biochemistry at Heidelberg University Biochemistry Center (BZH) |
| 2002 | Call for a professorship for Pharmaceutical Chemistry (Marburg), declined |
| since 2003 | Professor for Biochemistry at Heidelberg University Biochemistry Center (BZH) |
| German representative of COST Action CM0801 of the EU on “New drugs for neglected diseases” |
Lab Members
Mitarbeiter/-innen
Publications
Synthesis and Biological Evaluation of Natural-Product-Inspired, Aminoalkyl-Substituted 1-Benzopyrans as Novel Antiplasmodial Agents. J Med Chem. 2021 May 13;64(9):6397-6409. doi: 10.1021/acs.jmedchem.1c00483. Epub 2021 Apr 26. PMID: 33901399
Uth JF, Börgel F, Lehmkuhl K, Schepmann D, Kaiser M, Jabor VAP, Nonato MC, Krauth-Siegel RL, Schmidt TJ, Wünsch B. (2021)
A glutaredoxin in the mitochondrial intermembrane space has stage-specific functions in the thermo-tolerance and proliferation of African trypanosomes. Redox Biology 15, 532-547.
Ebersoll, S., Musunda, B., Schmenger, T., Dirdjaja, N., Bonilla, M., Manta, B., Ulrich, K., Comini, M. A., and Krauth-Siegel, R. L. (2018)
Biological evaluation and X-ray co-crystal structures of cyclohexylpyrrolidine ligands for trypanothione reductase (TR), an enzyme from the redox metabolism of Trypanosoma. Chem. Med. Chem. 13, 957-967.
De Gasparo, R., Persch, E., Bryson, S. Hentzen, N., Kaiser, M., Pai, E. F., Krauth-Siegel, R. L., and Diederich, F. (2018)
Backbone NMR assignments of tryparedoxin, the central protein in the hydroperoxide detoxification cascade of African trypanosomes, in the oxidized and reduced form. Biomol NMR Assign. 11, 193-196.
Wagner, A., Diehl, E., Krauth-Siegel, R. L. and Hellmich, U. A. (2017)
Bistacrines as potential antitrypanosomal agents. Bioorg. Med. Chem. 25, 4526-4531.
Schmidt, I., Göllner, S., Fuß, A., Stich, A., Kucharski, A., Schirmeister, T., Katzowitsch, E., Bruhn, H., Miliu, A., Krauth-Siegel, R. L., Holzgrabe, U. (2017)
Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display activity against Trypanosoma brucei parasites. Eur. J. Med. Chem. 141, 138-148.
Uliassi, E. Fiorani, G., Krauth-Siegel, R. L., Bergamini, C., Fato, R., Bianchini, G., Menéndez, J. C., Molina, M. T., López-Montero, E., Falchi, F., Cavalli, A., Gul, S., Kuzikov, M., Ellinger, B., Moraes, C. B., Freitas-Junior, L. H., Borsari, C., Costi, M. P. and Bolognesi, M. L. (2017)
Development of novel peptide-based Michael acceptors targeting rhodesain and falcipain-2 for the treatment of neglected tropical diseases (NTDs). J. Med. Chem. 60, 6911-6923.
Previti, S., Ettari, R., Cosconati, S., Amendola, G., Chouchene, K., Wagner, A., Hellmich, U. A., Ulrich, K., Krauth-Siegel, R. L., Wich, P. R., Schmid, I., Schirmeister, T., Gut, J., Rosenthal, P. J., Grasso, S. and Zapalà, M. (2017)
Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei. Bioorg. Med. Chem. Lett. 27, 45-50.
Schirmeister, T., Schmitz, J., Jung, S., Schmenger, T., Krauth-Siegel, R. L. and Gütschow, M. (2017)
Stress-induced protein S-glutathionylation and S-trypanothiolation in African trypanosomes – a quantitative redox proteome and thiol analysis. Antiox. Redox Sign. 27, 517-533.
Ulrich, K., Finkenzeller, C., Merker, S., Rojas, F., Matthews, K., Ruppert, T. and Krauth-Siegel, R. L. (2017)
Synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates. Bioorg. Med. Chem. 25, 84-90.
Jagu, E., Pomel, S., Díez-Martínez, A., Ramiandrasoa, F., Krauth-Siegel, R. L., Pethe, S., Blonski, C., Labruère, R. and Loiseau, P. M. (2017)
Trypanocidal activity of quinoxaline 1,4 di-N-oxide derivatives as trypanothione reductase inhibitors. Molecules 22, 220
Chacón-Vargas, K. F., Nogueda-Torres, B.; Sánchez-Torres, L. E., Suarez-Contreras, E., Villalobos-Rocha, J. C., Torres-Martinez, Y., Lara-Ramirez, E. E., Fiorani, G., Krauth-Siegel, R. L., Bolognesi, M. L., Monge, A., Rivera, G. (2017)
Catalytic properties, localization, and in vivo role of Px IV, a novel tryparedoxin peroxidase of Trypanosoma brucei. Mol. Biochem. Parasitol. 207, 84-88.
Liu, I., Bogacz, M., Schaffroth, C., Dirdjaja, N., and Krauth-Siegel, R. L. (2016)
Dipeptidyl nitroalkenes as potent reversible inhibitors of cysteine proteases rhodesain and cruzain. ACS Medic. Chem. Letters 7, 1073-1076.
Latorre, A., Schirmeister, T., Kesselring, J., Jung, S., Johé, P., Hellmich, U. A., Heilos, A., Engels, B., Krauth-Siegel, R. L., Dirdjaja, N., Bou-Iserte, L., Rodríguez, S. and González, F. V. (2016)
In vitro and in vivo identification of tetradentated polyamine complexes as highly efficient metallodrugs against Trypanosoma cruzi. Exp. Parasitol. 164, 20-30.
Olmo, F., Cussó, O., Marín, C., Rosales, M. J., Urbonová, K., Krauth-Siegel, R. L., Costas, M., Ribas, X. and Sánchez-Moreno, M. (2016)
Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase. Eur. J. Med. Chem. 108, 436-443.
Marcu, A., Schurigt, U., Müller, K., Moll, H., Krauth-Siegel, R. L. and Prinz, H. (2016)
The cytosolic or the mitochondrial glutathione peroxidase-type tryparedoxin peroxidase is sufficient to protect procyclic Trypanosoma brucei from iron-mediated mitochondrial damage and lysis. Mol. Microbiol. 99, 172-187.
Schaffroth, C., Bogacz, M., Dirdjaja, N., Nissen, A. and Krauth-Siegel, R. L. (2016)
Thiol redox biology of trypanosomatids and potential targets for chemotherapy. Mol. Biochem. Parasitol. 206, 67-74. Leroux, A. and Krauth-Siegel, R. L. (2016)
Detection of thiol-based switch processes in parasites – facts and future. Biol. Chem. 396, 445-463.
Rahbari, M., Diederich, K., Becker, K., Krauth-Siegel, R. L. and Jortzik, E. (2015)
Glutaredoxin-deficiency confers bloodstream Trypanosoma brucei with improved thermotolerance. Mol. Biochem. Parasitol. 204, 93-105.
Musunda, B., Benítez, D., Dirdjaja, N., Comini, M. A. and Krauth-Siegel, R. L. (2015)
Trypanothione reductase: A target protein for a combined in vitro and in silico screening approach. PLoS Negl. Trop. Dis. 9(6): e0003773.
Beig, M., Oellien, F., Garoff, L., Noack, S., Krauth-Siegel, R. L. and Selzer, P. M. (2015)
Binding to large enzyme pockets: Small-molecule inhibitors of trypanothione reductase. Chem. Med. Chem. 9, 1880-1891.
Persch, E., Bryson, S., Todoroff, N. K., Eberle, C., Thelemann, J., Dirdjaja, N., Kaiser, M., Weber, M., Derbani, H., Brun, R., Schneider, G., Pai, E. F., Krauth-Siegel, R. L. and Diederich, F. (2014)
Cytosolic peroxidases protect the lysosome of bloodstream African trypanosomes from iron-mediated membrane damage. PLoS Pathogens e1004075.
Hiller, C., Nissen, A., Benítez, D., Comini, M. A. and Krauth-Siegel, R. L. (2014)
Toward the development of dual-targeted glyceraldehyde-3-phosphate dehydrogenase/trypanothione reductase inhibitors against Trypanosoma brucei and Trypanosoma cruzi. Chem. Med. Chem. 9, 371-382.
Belluti, F., Uliassi, E., Veronesi, G., Bergamini, C., Kaiser, M., Brun, R., Viola, A., Fato, R., Michels, P. A. M., Krauth-Siegel, R. L., Cavalli, A. and Bolognesi, M. L. (2014)
Dissecting the catalytic mechanism of Trypanosoma brucei trypanothione synthetase by kinetic analysis and computational modelling. J. Biol. Chem. 288, 23751-23764.
Leroux, A.L., Haanstra, J. R., Bakker, B. M. and Krauth-Siegel, R. L. (2013)
Iron-sulfur cluster (ISC) binding by mitochondrial monothiol glutaredoxin-1 of Trypanosoma brucei: molecular basis of ISC coordination and relevance for parasite infectivity. Antiox. Redox Sign. 19, 665-682.
Manta, B., Pavan, C., Sturlese, M., Medeiros, A., Crispo, M., Berndt, C., Krauth-Siegel, R. L., Bellanda, M. and Comini, M. A. (2013)
Mono- and dithiol glutaredoxins in the trypanothione-based redox metabolism of pathogenic trypanosomes. Antiox. Redox Sign. 19, 708-722.
Comini, M. A., Krauth-Siegel, R. L. and Bellanda, M. (2013)
Bioinformatic and experimental fishing for artemisinin-interacting proteins from human nasopharyngeal cancer cells. Mol Biosyst. 8(4):1311-8.
Eichhorn T, Schloissnig S, Hahn B, Wendler A, Mertens R, Lehmann WD, Krauth-Siegel RL, Efferth T. (2012)
Conjugation of quinones with natural polyamines: toward an expanded antitrypanosomatid profile. J Med Chem. 55(23):10490-500.
Lizzi F, Veronesi G, Belluti F, Bergamini C, López-Sánchez A, Kaiser M, Brun R, Krauth-Siegel RL, Hall DG, Rivas L, Bolognesi ML. (2012)
High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin. J Biol Chem. 287(12):8792-802.
Fueller F, Jehle B, Putzker K, Lewis JD, Krauth-Siegel RL. (2012)
Low-molecular-mass antioxidants in parasites. Antioxid Redox Signal. 17(4):583-607.
Krauth-Siegel RL, Leroux AE. (2012)
A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage. Free Radic. Biol. Med. 51, 856-868.
Diechtierow, M. and Krauth-Siegel, R.L. (2011)
Improved inhibitors of trypanothione reductase by combination of motifs: Synthesis, inhibitory potency, binding mode, and antiprotozoal activities. Chem. Med. Chem. 6, 292-301.
Eberle, C., Lauber, B. S., Fankhausen, D., Kaiser, M., Brun, R., Krauth-Siegel, R. L. and Diederich, F. (2011)
Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei. Mol. Microbiol. 81, 623-639.
Roldán, A., Comini, M. A., Crispo, M., and Krauth-Siegel, R. L. (2011)
The conserved Cys76 plays a crucial role for the conformation of reduced glutathione peroxidase-type tryparedoxin peroxidase. FEBS Lett. 584(5):1027-32.
Muhle-Goll C, Füller F, Ulrich AS, Krauth-Siegel RL. (2010)
The dithiol glutaredoxins of african trypanosomes have distinct roles and are closely linked to the unique trypanothione metabolism. J Biol Chem. 285(45):35224-37.
Ceylan S, Seidel V, Ziebart N, Berndt C, Dirdjaja N, Krauth-Siegel RL. (2010)
The silicon trypanosome. Parasitology. 137(9):1333-41. Review.
Bakker BM, Krauth-Siegel RL, Clayton C, Matthews K, Girolami M, Westerhoff HV, Michels PA, Breitling R, Barrett MP. (2010)
(editors: Jacob BC and Winyard PG), book review in ChemMedChem. 4:2123-2127.
Krauth-Siegel RL. Redox signaling and regulation in biology and medicine. (2009)
2,3-diphenyl-1,4-naphthoquinone: a potential chemotherapeutic agent against Trypanosoma cruzi. J Parasitol. 95(2):461-6.
Ramos EI, Garza KM, Krauth-Siegel RL, Bader J, Martinez LE, Maldonado RA. (2009)
Glyoxalase II does not support methylglyoxal detoxification but serves as a general trypanothione thioesterase in African trypanosomes. Mol Biochem Parasitol. 163(1):19-27.
Wendler A, Irsch T, Rabbani N, Thornalley PJ, Krauth-Siegel RL. (2009)
Pentafluorosulfanyl as a novel building block for enzyme inhibitors: trypanothione reductase inhibition and antiprotozoal activities of diarylamines. Chembiochem. 10(1):79-83.
Stump B, Eberle C, Schweizer WB, Kaiser M, Brun R, Krauth-Siegel RL, Lentz D, Diederich F. (2009)
Preparative enzymatic synthesis of trypanothione and trypanothione analogues. Int J Parasitol. 39(10):1059-62.
Comini MA, Dirdjaja N, Kaschel M, Krauth-Siegel RL. (2009)
Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase. Bioorg Med Chem Lett. 19(11):3031-5.
Cavalli A, Lizzi F, Bongarzone S, Brun R, Luise Krauth-Siegel R, Bolognesi ML. (2009)
Synthesis, inhibition potency, binding mode, and antiprotozoal activities of fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated diaryl sulfide scaffolds. ChemMedChem. 4(12):2034-44.
Eberle C, Burkhard JA, Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. (2009)
Unsaturated Mannich bases active against multidrug-resistant Trypanosoma brucei brucei strains. ChemMedChem, 4(3), 339–351. https://doi.org/10.1002/cmdc.200800360 Wenzel, I. N., Wong, P. E., Maes, L., Müller, T. J., Krauth-Siegel, R. L., Barrett, M. P., & Davioud-Charvet, E. (2009)
1H, 13C, and 15N assignment of the oxidized and reduced forms of T. brucei glutathione peroxidase-type tryparedoxin peroxidase. Biomolecular NMR Assignments. 2:65-68.
Melchers J, Krauth-Siegel RL, Muhle-Goll C. (2008)
Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1. Biol Chem. 389(1):21-32.
Filser M, Comini MA, Molina-Navarro MM, Dirdjaja N, Herrero E, Krauth-Siegel RL. (2008)
Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products. Mol Biochem Parasitol. 160(1):65-9. Buchholz K, Comini MA, Wissenbach D, Schirmer RH, Krauth-Siegel RL, Gromer S. (2008)
Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities. Org Biomol Chem. 6(21):3935-47.
Stump B, Eberle C, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. (2008)
Monothiol glutaredoxin-1 is an essential iron-sulfur protein in the mitochondrion of African trypanosomes. J Biol Chem. 283(41):27785-98.
Comini MA, Rettig J, Dirdjaja N, Hanschmann EM, Berndt C, Krauth-Siegel RL. (2008)
Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim Biophys Acta. 1780(11):1236-48. Review.
Krauth-Siegel RL, Comini MA. (2008)
Structural basis for a distinct catalytic mechanism in Trypanosoma brucei tryparedoxin peroxidase. J Biol Chem. 283(44):30401-11. Melchers J, Diechtierow M, Fehér K, Sinning I, Tews I, Krauth-Siegel RL, Muhle-Goll C. (2008)
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. 5503-8.
Beig M, Bender F, Oellien F, Rohwer A, Gaßel M, Selzer P, Unden G, Krauth-Siegel RL. (2008)
Betraying the Parasite's Redox System: Diaryl Sulfide-Based Inhibitors of Trypanothione Reductase: Subversive Substrates and Antitrypanosomal Properties. ChemMedChem. 2(12):1708-1712.
Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. (2007)
Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei. Biochem J. 405(3):445-54.
Schlecker T, Comini MA, Melchers J, Ruppert T, Krauth-Siegel RL. (2007)
Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes. Biochem J. 402(1):43-9.
Comini MA, Krauth-Siegel RL, Flohé L. (2007)
Glutathionylation of trypanosomal thiol redox proteins. J Biol Chem. 282(12):8678-94.
Melchers J, Dirdjaja N, Ruppert T, Krauth-Siegel RL. (2007)
The trypanothione system. Subcell Biochem. 44:231-51.
Krauth-Siegel LR, Comini MA, Schlecker T. (2007)
Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets. J Med Chem. 49(11):3322-31.
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. (2006)
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. 44(5):690-715. Krauth-Siegel RL, Bauer H, Schirmer RH. (2005)
Dithiolproteine als Hüter des intrazellulären Redoxmilieus bei Parasiten: alte und neue Wirkstoff-Targets bei Trypanosomiasis und Malaria. Angew Chem. 117:698-724. Krauth-Siegel RL, Bauer H, Schirmer RH. (2005)
Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis. J Med Chem. 48(15):4793-802.
Meiering S, Inhoff O, Mies J, Vincek A, Garcia G, Kramer B, Dormeyer M, Krauth-Siegel RL. (2005)
Irreversible inactivation of trypanothione reductase by unsaturated mannich bases: a divinyl ketone as key intermediate. J Med Chem. 48(23):7400-10. Lee B, Bauer H, Melchers J, Ruppert T, Rattray L, Yardley V, Davioud-Charvet E, Krauth-Siegel RL. (2005)
Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei. J Biol Chem. 280(15):14385-94.
Schlecker T, Schmidt A, Dirdjaja N, Voncken F, Clayton C, Krauth-Siegel RL. (2005)
The crystal structure of Plasmodium falciparum glutamate dehydrogenase, a putative target for novel antimalarial drugs. J Mol Biol. 349(3):597-607.
Werner C, Stubbs MT, Krauth-Siegel RL, Klebe G. (2005)
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. 867–76. Krauth-Siegel RL, Davioud-Charvet E. (2005)
Glyoxalase II of African trypanosomes is trypanothione-dependent. J Biol Chem. 279(21):22209-17.
Irsch T, Krauth-Siegel RL. (2004)
Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei. J Biol Chem. 278(47): 46329-36.
Schmidt H, Krauth-Siegel RL. (2003)
Parasite-specific trypanothione reductase as a drug target molecule. Parasitol Res. 90 Suppl 2: 77-85.
Krauth-Siegel RL, Inhoff O. (2003)
Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers. Free Radic Res. 37(3):281-91.
Gutierrez-Correa J, Krauth-Siegel RL, Stoppani AO. (2003)
Structure of thioredoxin from Trypanosoma brucei brucei. FEBS Lett. 554:301-305.
Friemann R, Schmidt H, Ramaswamy S, Forstner M, Krauth-Siegel RL, Eklund H. (2003)
The parasite-specific trypanothione metabolism of trypanosoma and leishmania. Biol Chem. 384(4):539-49.
Krauth-Siegel RL, Meiering SK, Schmidt H. (2003)
Thiol-based redox metabolism of protozoan parasites. Trends Parasitol. 19(7):320-8.
Müller S, Liebau E, Walter RD, Krauth-Siegel RL. (2003)
Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. J. Biol. Chem. 277, 17548-17555.
Reckenfelderbäumer, N., Krauth-Siegel, RL. (2002)
Coupling of a competitive and an irreversible ligand generates mixed type inhibitors of Trypanosoma cruzi trypanothione reductase. J. Med. Chem. 45, 4524-4530.
Inhoff, O., Richards, J. M., Briet, J. W., Lowe, G., Krauth-Siegel, RL. (2002)
Der parasitäre Trypanothion-Stoffwechsel-einzigartig und lebensnotwendig. BIOforum. 7-8:478-480.
Schmidt H., Schmidt A., Krauth-Siegel RL. (2002)
Enzymes of the trypanothione metabolism as targets for antitrypanosomal drug development. Current Topics Med. Chem. 2, 1239-1259.
Schmidt, A., Krauth-Siegel, R. L. (2002)
Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator deferoxamine. Int J Parasitol. 32(4):473-9.
Breidbach T, Scory S, Krauth-Siegel RL, Steverding D. (2002)
Overexpression of the putative thiol conjugate transporter TbMRPA causes melarsoprol resistance in Trypanosoma brucei. Mol Microbiol. 43(5):1129-38.
Shahi SK, Krauth-Siegel RL, Clayton CE. (2002)
Silencing of the thioredoxin gene in Trypanosoma brucei brucei. Mol. Biochem. Parasitol. 125:207-210
Schmidt A, Clayton C, Krauth-Siegel RL. (2002)
The crystal structure of lipoamide dehydrogenase from Trypanosoma cruzi: A target for the design of new drugs against Chagas’ disease. Flavins and Flavoproteins :917-922
Werner C, Stubbs MT, Klebe G, Krauth-Siegel RL. (2002)
Trypanothione and tryparedoxin in ribonucleotide reduction. Methods Enzymol. 347:259-66.
Krauth-Siegel RL, Schmidt H. (2002)
2- and 3-substituted-1,4-naphthoquinone derivatives as subversive substrates of trypanothione reductase and lipoamide dehydrogenase from Trypanosoma cruzi: synthesis and correlation between redox-cycling activities and in vitro cytotoxicity. J. Med. Chem. 44:548–65. Salmon-Chemin L, Buisine E, Yardley V, Kohler S, Debreu MA, Landry V, Sergheraert C, Croft SL, Krauth-Siegel LR, Davioud-Charvet E. (2001)
Trypanothione-dependent synthesis of deoxyribonucleotides by Trypanosoma brucei ribonucleotide reductase. J. Biol. Chem. 276, 10602-10606.
Dormeyer, M., Reckenfelderbäumer, N., Lüdemann, H., Krauth-Siegel, RL. (2001)
Disulfide-reductase inhibitors as chemotherapeutic agents: The design of drugs for trypanosomiasis and malaria. Angew Chem Int Ed Engl 34, 141-154 Schirmer RH, Müller JG & Krauth-Siegel RL (1995)
Uth JF, Börgel F, Lehmkuhl K, Schepmann D, Kaiser M, Jabor VAP, Nonato MC, Krauth-Siegel RL, Schmidt TJ, Wünsch B. (2021)
A glutaredoxin in the mitochondrial intermembrane space has stage-specific functions in the thermo-tolerance and proliferation of African trypanosomes. Redox Biology 15, 532-547.
Ebersoll, S., Musunda, B., Schmenger, T., Dirdjaja, N., Bonilla, M., Manta, B., Ulrich, K., Comini, M. A., and Krauth-Siegel, R. L. (2018)
Biological evaluation and X-ray co-crystal structures of cyclohexylpyrrolidine ligands for trypanothione reductase (TR), an enzyme from the redox metabolism of Trypanosoma. Chem. Med. Chem. 13, 957-967.
De Gasparo, R., Persch, E., Bryson, S. Hentzen, N., Kaiser, M., Pai, E. F., Krauth-Siegel, R. L., and Diederich, F. (2018)
Backbone NMR assignments of tryparedoxin, the central protein in the hydroperoxide detoxification cascade of African trypanosomes, in the oxidized and reduced form. Biomol NMR Assign. 11, 193-196.
Wagner, A., Diehl, E., Krauth-Siegel, R. L. and Hellmich, U. A. (2017)
Bistacrines as potential antitrypanosomal agents. Bioorg. Med. Chem. 25, 4526-4531.
Schmidt, I., Göllner, S., Fuß, A., Stich, A., Kucharski, A., Schirmeister, T., Katzowitsch, E., Bruhn, H., Miliu, A., Krauth-Siegel, R. L., Holzgrabe, U. (2017)
Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display activity against Trypanosoma brucei parasites. Eur. J. Med. Chem. 141, 138-148.
Uliassi, E. Fiorani, G., Krauth-Siegel, R. L., Bergamini, C., Fato, R., Bianchini, G., Menéndez, J. C., Molina, M. T., López-Montero, E., Falchi, F., Cavalli, A., Gul, S., Kuzikov, M., Ellinger, B., Moraes, C. B., Freitas-Junior, L. H., Borsari, C., Costi, M. P. and Bolognesi, M. L. (2017)
Development of novel peptide-based Michael acceptors targeting rhodesain and falcipain-2 for the treatment of neglected tropical diseases (NTDs). J. Med. Chem. 60, 6911-6923.
Previti, S., Ettari, R., Cosconati, S., Amendola, G., Chouchene, K., Wagner, A., Hellmich, U. A., Ulrich, K., Krauth-Siegel, R. L., Wich, P. R., Schmid, I., Schirmeister, T., Gut, J., Rosenthal, P. J., Grasso, S. and Zapalà, M. (2017)
Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei. Bioorg. Med. Chem. Lett. 27, 45-50.
Schirmeister, T., Schmitz, J., Jung, S., Schmenger, T., Krauth-Siegel, R. L. and Gütschow, M. (2017)
Stress-induced protein S-glutathionylation and S-trypanothiolation in African trypanosomes – a quantitative redox proteome and thiol analysis. Antiox. Redox Sign. 27, 517-533.
Ulrich, K., Finkenzeller, C., Merker, S., Rojas, F., Matthews, K., Ruppert, T. and Krauth-Siegel, R. L. (2017)
Synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates. Bioorg. Med. Chem. 25, 84-90.
Jagu, E., Pomel, S., Díez-Martínez, A., Ramiandrasoa, F., Krauth-Siegel, R. L., Pethe, S., Blonski, C., Labruère, R. and Loiseau, P. M. (2017)
Trypanocidal activity of quinoxaline 1,4 di-N-oxide derivatives as trypanothione reductase inhibitors. Molecules 22, 220
Chacón-Vargas, K. F., Nogueda-Torres, B.; Sánchez-Torres, L. E., Suarez-Contreras, E., Villalobos-Rocha, J. C., Torres-Martinez, Y., Lara-Ramirez, E. E., Fiorani, G., Krauth-Siegel, R. L., Bolognesi, M. L., Monge, A., Rivera, G. (2017)
Catalytic properties, localization, and in vivo role of Px IV, a novel tryparedoxin peroxidase of Trypanosoma brucei. Mol. Biochem. Parasitol. 207, 84-88.
Liu, I., Bogacz, M., Schaffroth, C., Dirdjaja, N., and Krauth-Siegel, R. L. (2016)
Dipeptidyl nitroalkenes as potent reversible inhibitors of cysteine proteases rhodesain and cruzain. ACS Medic. Chem. Letters 7, 1073-1076.
Latorre, A., Schirmeister, T., Kesselring, J., Jung, S., Johé, P., Hellmich, U. A., Heilos, A., Engels, B., Krauth-Siegel, R. L., Dirdjaja, N., Bou-Iserte, L., Rodríguez, S. and González, F. V. (2016)
In vitro and in vivo identification of tetradentated polyamine complexes as highly efficient metallodrugs against Trypanosoma cruzi. Exp. Parasitol. 164, 20-30.
Olmo, F., Cussó, O., Marín, C., Rosales, M. J., Urbonová, K., Krauth-Siegel, R. L., Costas, M., Ribas, X. and Sánchez-Moreno, M. (2016)
Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase. Eur. J. Med. Chem. 108, 436-443.
Marcu, A., Schurigt, U., Müller, K., Moll, H., Krauth-Siegel, R. L. and Prinz, H. (2016)
The cytosolic or the mitochondrial glutathione peroxidase-type tryparedoxin peroxidase is sufficient to protect procyclic Trypanosoma brucei from iron-mediated mitochondrial damage and lysis. Mol. Microbiol. 99, 172-187.
Schaffroth, C., Bogacz, M., Dirdjaja, N., Nissen, A. and Krauth-Siegel, R. L. (2016)
Thiol redox biology of trypanosomatids and potential targets for chemotherapy. Mol. Biochem. Parasitol. 206, 67-74. Leroux, A. and Krauth-Siegel, R. L. (2016)
Detection of thiol-based switch processes in parasites – facts and future. Biol. Chem. 396, 445-463.
Rahbari, M., Diederich, K., Becker, K., Krauth-Siegel, R. L. and Jortzik, E. (2015)
Glutaredoxin-deficiency confers bloodstream Trypanosoma brucei with improved thermotolerance. Mol. Biochem. Parasitol. 204, 93-105.
Musunda, B., Benítez, D., Dirdjaja, N., Comini, M. A. and Krauth-Siegel, R. L. (2015)
Trypanothione reductase: A target protein for a combined in vitro and in silico screening approach. PLoS Negl. Trop. Dis. 9(6): e0003773.
Beig, M., Oellien, F., Garoff, L., Noack, S., Krauth-Siegel, R. L. and Selzer, P. M. (2015)
Binding to large enzyme pockets: Small-molecule inhibitors of trypanothione reductase. Chem. Med. Chem. 9, 1880-1891.
Persch, E., Bryson, S., Todoroff, N. K., Eberle, C., Thelemann, J., Dirdjaja, N., Kaiser, M., Weber, M., Derbani, H., Brun, R., Schneider, G., Pai, E. F., Krauth-Siegel, R. L. and Diederich, F. (2014)
Cytosolic peroxidases protect the lysosome of bloodstream African trypanosomes from iron-mediated membrane damage. PLoS Pathogens e1004075.
Hiller, C., Nissen, A., Benítez, D., Comini, M. A. and Krauth-Siegel, R. L. (2014)
Toward the development of dual-targeted glyceraldehyde-3-phosphate dehydrogenase/trypanothione reductase inhibitors against Trypanosoma brucei and Trypanosoma cruzi. Chem. Med. Chem. 9, 371-382.
Belluti, F., Uliassi, E., Veronesi, G., Bergamini, C., Kaiser, M., Brun, R., Viola, A., Fato, R., Michels, P. A. M., Krauth-Siegel, R. L., Cavalli, A. and Bolognesi, M. L. (2014)
Dissecting the catalytic mechanism of Trypanosoma brucei trypanothione synthetase by kinetic analysis and computational modelling. J. Biol. Chem. 288, 23751-23764.
Leroux, A.L., Haanstra, J. R., Bakker, B. M. and Krauth-Siegel, R. L. (2013)
Iron-sulfur cluster (ISC) binding by mitochondrial monothiol glutaredoxin-1 of Trypanosoma brucei: molecular basis of ISC coordination and relevance for parasite infectivity. Antiox. Redox Sign. 19, 665-682.
Manta, B., Pavan, C., Sturlese, M., Medeiros, A., Crispo, M., Berndt, C., Krauth-Siegel, R. L., Bellanda, M. and Comini, M. A. (2013)
Mono- and dithiol glutaredoxins in the trypanothione-based redox metabolism of pathogenic trypanosomes. Antiox. Redox Sign. 19, 708-722.
Comini, M. A., Krauth-Siegel, R. L. and Bellanda, M. (2013)
Bioinformatic and experimental fishing for artemisinin-interacting proteins from human nasopharyngeal cancer cells. Mol Biosyst. 8(4):1311-8.
Eichhorn T, Schloissnig S, Hahn B, Wendler A, Mertens R, Lehmann WD, Krauth-Siegel RL, Efferth T. (2012)
Conjugation of quinones with natural polyamines: toward an expanded antitrypanosomatid profile. J Med Chem. 55(23):10490-500.
Lizzi F, Veronesi G, Belluti F, Bergamini C, López-Sánchez A, Kaiser M, Brun R, Krauth-Siegel RL, Hall DG, Rivas L, Bolognesi ML. (2012)
High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin. J Biol Chem. 287(12):8792-802.
Fueller F, Jehle B, Putzker K, Lewis JD, Krauth-Siegel RL. (2012)
Low-molecular-mass antioxidants in parasites. Antioxid Redox Signal. 17(4):583-607.
Krauth-Siegel RL, Leroux AE. (2012)
A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage. Free Radic. Biol. Med. 51, 856-868.
Diechtierow, M. and Krauth-Siegel, R.L. (2011)
Improved inhibitors of trypanothione reductase by combination of motifs: Synthesis, inhibitory potency, binding mode, and antiprotozoal activities. Chem. Med. Chem. 6, 292-301.
Eberle, C., Lauber, B. S., Fankhausen, D., Kaiser, M., Brun, R., Krauth-Siegel, R. L. and Diederich, F. (2011)
Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei. Mol. Microbiol. 81, 623-639.
Roldán, A., Comini, M. A., Crispo, M., and Krauth-Siegel, R. L. (2011)
The conserved Cys76 plays a crucial role for the conformation of reduced glutathione peroxidase-type tryparedoxin peroxidase. FEBS Lett. 584(5):1027-32.
Muhle-Goll C, Füller F, Ulrich AS, Krauth-Siegel RL. (2010)
The dithiol glutaredoxins of african trypanosomes have distinct roles and are closely linked to the unique trypanothione metabolism. J Biol Chem. 285(45):35224-37.
Ceylan S, Seidel V, Ziebart N, Berndt C, Dirdjaja N, Krauth-Siegel RL. (2010)
The silicon trypanosome. Parasitology. 137(9):1333-41. Review.
Bakker BM, Krauth-Siegel RL, Clayton C, Matthews K, Girolami M, Westerhoff HV, Michels PA, Breitling R, Barrett MP. (2010)
(editors: Jacob BC and Winyard PG), book review in ChemMedChem. 4:2123-2127.
Krauth-Siegel RL. Redox signaling and regulation in biology and medicine. (2009)
2,3-diphenyl-1,4-naphthoquinone: a potential chemotherapeutic agent against Trypanosoma cruzi. J Parasitol. 95(2):461-6.
Ramos EI, Garza KM, Krauth-Siegel RL, Bader J, Martinez LE, Maldonado RA. (2009)
Glyoxalase II does not support methylglyoxal detoxification but serves as a general trypanothione thioesterase in African trypanosomes. Mol Biochem Parasitol. 163(1):19-27.
Wendler A, Irsch T, Rabbani N, Thornalley PJ, Krauth-Siegel RL. (2009)
Pentafluorosulfanyl as a novel building block for enzyme inhibitors: trypanothione reductase inhibition and antiprotozoal activities of diarylamines. Chembiochem. 10(1):79-83.
Stump B, Eberle C, Schweizer WB, Kaiser M, Brun R, Krauth-Siegel RL, Lentz D, Diederich F. (2009)
Preparative enzymatic synthesis of trypanothione and trypanothione analogues. Int J Parasitol. 39(10):1059-62.
Comini MA, Dirdjaja N, Kaschel M, Krauth-Siegel RL. (2009)
Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase. Bioorg Med Chem Lett. 19(11):3031-5.
Cavalli A, Lizzi F, Bongarzone S, Brun R, Luise Krauth-Siegel R, Bolognesi ML. (2009)
Synthesis, inhibition potency, binding mode, and antiprotozoal activities of fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated diaryl sulfide scaffolds. ChemMedChem. 4(12):2034-44.
Eberle C, Burkhard JA, Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. (2009)
Unsaturated Mannich bases active against multidrug-resistant Trypanosoma brucei brucei strains. ChemMedChem, 4(3), 339–351. https://doi.org/10.1002/cmdc.200800360 Wenzel, I. N., Wong, P. E., Maes, L., Müller, T. J., Krauth-Siegel, R. L., Barrett, M. P., & Davioud-Charvet, E. (2009)
1H, 13C, and 15N assignment of the oxidized and reduced forms of T. brucei glutathione peroxidase-type tryparedoxin peroxidase. Biomolecular NMR Assignments. 2:65-68.
Melchers J, Krauth-Siegel RL, Muhle-Goll C. (2008)
Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1. Biol Chem. 389(1):21-32.
Filser M, Comini MA, Molina-Navarro MM, Dirdjaja N, Herrero E, Krauth-Siegel RL. (2008)
Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products. Mol Biochem Parasitol. 160(1):65-9. Buchholz K, Comini MA, Wissenbach D, Schirmer RH, Krauth-Siegel RL, Gromer S. (2008)
Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities. Org Biomol Chem. 6(21):3935-47.
Stump B, Eberle C, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. (2008)
Monothiol glutaredoxin-1 is an essential iron-sulfur protein in the mitochondrion of African trypanosomes. J Biol Chem. 283(41):27785-98.
Comini MA, Rettig J, Dirdjaja N, Hanschmann EM, Berndt C, Krauth-Siegel RL. (2008)
Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim Biophys Acta. 1780(11):1236-48. Review.
Krauth-Siegel RL, Comini MA. (2008)
Structural basis for a distinct catalytic mechanism in Trypanosoma brucei tryparedoxin peroxidase. J Biol Chem. 283(44):30401-11. Melchers J, Diechtierow M, Fehér K, Sinning I, Tews I, Krauth-Siegel RL, Muhle-Goll C. (2008)
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. 5503-8.
Beig M, Bender F, Oellien F, Rohwer A, Gaßel M, Selzer P, Unden G, Krauth-Siegel RL. (2008)
Betraying the Parasite's Redox System: Diaryl Sulfide-Based Inhibitors of Trypanothione Reductase: Subversive Substrates and Antitrypanosomal Properties. ChemMedChem. 2(12):1708-1712.
Stump B, Kaiser M, Brun R, Krauth-Siegel RL, Diederich F. (2007)
Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei. Biochem J. 405(3):445-54.
Schlecker T, Comini MA, Melchers J, Ruppert T, Krauth-Siegel RL. (2007)
Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes. Biochem J. 402(1):43-9.
Comini MA, Krauth-Siegel RL, Flohé L. (2007)
Glutathionylation of trypanosomal thiol redox proteins. J Biol Chem. 282(12):8678-94.
Melchers J, Dirdjaja N, Ruppert T, Krauth-Siegel RL. (2007)
The trypanothione system. Subcell Biochem. 44:231-51.
Krauth-Siegel LR, Comini MA, Schlecker T. (2007)
Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets. J Med Chem. 49(11):3322-31.
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. (2006)
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. 44(5):690-715. Krauth-Siegel RL, Bauer H, Schirmer RH. (2005)
Dithiolproteine als Hüter des intrazellulären Redoxmilieus bei Parasiten: alte und neue Wirkstoff-Targets bei Trypanosomiasis und Malaria. Angew Chem. 117:698-724. Krauth-Siegel RL, Bauer H, Schirmer RH. (2005)
Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis. J Med Chem. 48(15):4793-802.
Meiering S, Inhoff O, Mies J, Vincek A, Garcia G, Kramer B, Dormeyer M, Krauth-Siegel RL. (2005)
Irreversible inactivation of trypanothione reductase by unsaturated mannich bases: a divinyl ketone as key intermediate. J Med Chem. 48(23):7400-10. Lee B, Bauer H, Melchers J, Ruppert T, Rattray L, Yardley V, Davioud-Charvet E, Krauth-Siegel RL. (2005)
Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei. J Biol Chem. 280(15):14385-94.
Schlecker T, Schmidt A, Dirdjaja N, Voncken F, Clayton C, Krauth-Siegel RL. (2005)
The crystal structure of Plasmodium falciparum glutamate dehydrogenase, a putative target for novel antimalarial drugs. J Mol Biol. 349(3):597-607.
Werner C, Stubbs MT, Krauth-Siegel RL, Klebe G. (2005)
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. 867–76. Krauth-Siegel RL, Davioud-Charvet E. (2005)
Glyoxalase II of African trypanosomes is trypanothione-dependent. J Biol Chem. 279(21):22209-17.
Irsch T, Krauth-Siegel RL. (2004)
Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei. J Biol Chem. 278(47): 46329-36.
Schmidt H, Krauth-Siegel RL. (2003)
Parasite-specific trypanothione reductase as a drug target molecule. Parasitol Res. 90 Suppl 2: 77-85.
Krauth-Siegel RL, Inhoff O. (2003)
Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers. Free Radic Res. 37(3):281-91.
Gutierrez-Correa J, Krauth-Siegel RL, Stoppani AO. (2003)
Structure of thioredoxin from Trypanosoma brucei brucei. FEBS Lett. 554:301-305.
Friemann R, Schmidt H, Ramaswamy S, Forstner M, Krauth-Siegel RL, Eklund H. (2003)
The parasite-specific trypanothione metabolism of trypanosoma and leishmania. Biol Chem. 384(4):539-49.
Krauth-Siegel RL, Meiering SK, Schmidt H. (2003)
Thiol-based redox metabolism of protozoan parasites. Trends Parasitol. 19(7):320-8.
Müller S, Liebau E, Walter RD, Krauth-Siegel RL. (2003)
Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. J. Biol. Chem. 277, 17548-17555.
Reckenfelderbäumer, N., Krauth-Siegel, RL. (2002)
Coupling of a competitive and an irreversible ligand generates mixed type inhibitors of Trypanosoma cruzi trypanothione reductase. J. Med. Chem. 45, 4524-4530.
Inhoff, O., Richards, J. M., Briet, J. W., Lowe, G., Krauth-Siegel, RL. (2002)
Der parasitäre Trypanothion-Stoffwechsel-einzigartig und lebensnotwendig. BIOforum. 7-8:478-480.
Schmidt H., Schmidt A., Krauth-Siegel RL. (2002)
Enzymes of the trypanothione metabolism as targets for antitrypanosomal drug development. Current Topics Med. Chem. 2, 1239-1259.
Schmidt, A., Krauth-Siegel, R. L. (2002)
Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator deferoxamine. Int J Parasitol. 32(4):473-9.
Breidbach T, Scory S, Krauth-Siegel RL, Steverding D. (2002)
Overexpression of the putative thiol conjugate transporter TbMRPA causes melarsoprol resistance in Trypanosoma brucei. Mol Microbiol. 43(5):1129-38.
Shahi SK, Krauth-Siegel RL, Clayton CE. (2002)
Silencing of the thioredoxin gene in Trypanosoma brucei brucei. Mol. Biochem. Parasitol. 125:207-210
Schmidt A, Clayton C, Krauth-Siegel RL. (2002)
The crystal structure of lipoamide dehydrogenase from Trypanosoma cruzi: A target for the design of new drugs against Chagas’ disease. Flavins and Flavoproteins :917-922
Werner C, Stubbs MT, Klebe G, Krauth-Siegel RL. (2002)
Trypanothione and tryparedoxin in ribonucleotide reduction. Methods Enzymol. 347:259-66.
Krauth-Siegel RL, Schmidt H. (2002)
2- and 3-substituted-1,4-naphthoquinone derivatives as subversive substrates of trypanothione reductase and lipoamide dehydrogenase from Trypanosoma cruzi: synthesis and correlation between redox-cycling activities and in vitro cytotoxicity. J. Med. Chem. 44:548–65. Salmon-Chemin L, Buisine E, Yardley V, Kohler S, Debreu MA, Landry V, Sergheraert C, Croft SL, Krauth-Siegel LR, Davioud-Charvet E. (2001)
Trypanothione-dependent synthesis of deoxyribonucleotides by Trypanosoma brucei ribonucleotide reductase. J. Biol. Chem. 276, 10602-10606.
Dormeyer, M., Reckenfelderbäumer, N., Lüdemann, H., Krauth-Siegel, RL. (2001)
Disulfide-reductase inhibitors as chemotherapeutic agents: The design of drugs for trypanosomiasis and malaria. Angew Chem Int Ed Engl 34, 141-154 Schirmer RH, Müller JG & Krauth-Siegel RL (1995)
Collaborations
Collaborations exist with
- Prof. Paul Selzer, Intervet Company, Schwabenheim
- Prof. Francois Diederich, ETH Zürich
- Prof. Gerhard Klebe, Marburg University
- Dr. Marcelo Comini, Pasteur Institut Montevideo, Uruguay
- Dr. Simon Croft, LSHTM, London
- Prof. Reto Brun, STI, Basel
Funding
Our work is supported by the Deutsche Forschungsgemeinschaft,
DFG Kr 1242/1-4 and
SFB 544 "Control of tropical infectious diseases".
Contact
Heidelberg University
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Office:
+49 6221 54-4187 Lab:
+49 6221 54-4174 Fax:
+49 6221 54-5586 E-Mail:
luise.krauth-siegel@bzh.uni-heidelberg.de