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2could be produced recombinantly and is now available for detailed investigations. Prof.Graham Coombs from the University of Glasgow gave a lecture on the potential of proteasesas central targets for drug development against trypanosomatids. In particular, he criticallyanalyzed the different groups of cysteine peptidases with respect to their suitability. WhileGPI-protein transamidases, metacaspases and pyroglutamyl peptidases appeared lesssuitable, the ATG4.2 cysteine peptidase seemed to be a good drug target. Cysteine proteaseB (CPB) is already an evaluated molecule and is used in high-throughput screening forpotential inhibitors. Dr. Mike Blackman from the National Institute for Medical Research atMill Hill London informed us on Plasmodia merozoite proteases as targets against theparasite. He showed that surface proteins of stages penetrating the host cell are beingshaved off during this procedure by PfSUB2, a subtilisin-like serine protease. Furthermore,the existence of a second proteolytic activity which cleaves surface proteins within thecytoplasmic membrane could be shown.The topic of the first session was biosynthetic pathways as potential targets forantimalarial drug development. Dr. Sylke Müller from the University of Glasgow reported onthioredoxin reductase of Plasmodium falciparum, its catalytic mechanism and inhibition byorganotellurides. Dr. Jochen Wiesner and Dr. Hassan Jomaa from the Justus-LiebigUniversity Giessen reported on enzymes of the isoprenoid biosynthesis of Plasmodiumfalciparum as targets, and on the potential of Fosmidomycin in combination therapies to treatthe disease. Dr. Ivo Tews, University of Heidelberg, described the 1.7 angström highresolution3D structure of a glutaminase involved in vitamin B6 biosynthesis, which is notpresent in higher eukaryotes and therefore represents a suitable drug target.In the second session signal transduction pathways were discussed. Stefanie Boltefrom the BNI showed, using immunofluorescence of Plasmodium berghei-infectedhepatocytes, that MAPK1, a protein kinase of the parasite, co-localizes with antibodiesdirected against activated MAP kinases or phospho-tyrosine residues at the rim of theparasitophorous vacuole. A model was presented proposing that MAPK1 is activated by amitogen-activated protein kinase kinase (MEK) of the host cell. LmxMPK1, a mitogenactivatedprotein (MAP) kinase homologue from Leishmania mexicana, was presented as avalidated drug target against Leishmania by Inga Melzer from the BNI. The use of aninhibitor-sensitized LmxMPK1 for the establishment of a test system in vitro and in vivo wasdiscussed. Ulrike Schubert from Novoplant GmbH in Gatersleben reported on the influenceof calcium during invasion of Eimeria tenella sporozoites. Ryanodine, an agent derived fromthe plant Ryania speciosa inhibits calcium channels in the endoplasmatic reticulum of highereukaryotes and possibly of Eimeria, as preincubation of sporozoites led to a reduced
3invasion of MDBK cells. In her report on the development of resistance against miltefosine, adrug approved in India against Leishmaniasis, Kohelia Choudhury from the BNI talked abouta gene coding for a 299 kDa protein which was isolated in a screen of a cosmid library inLeishmania infantum under selection with miltefosine, thus conferring resistance.In the session on chemotherapy of helminths Dr. Markus Perbandt, University ofHamburg, presented the 3D-structure of the cytosolic glutathione S-transferase from theparasitic nematode Onchocerca volvulus, pointing out the possibility of structure-based drugdesign. Prof. Klaus Brehm from the University of Würzburg reported on signal transductioncascades of Echinococcus multilocularis presenting an in vitro culture system and discussedthe worm homologues to the kinases Raf und MKK as potential targets for drugdevelopment. Dr. Susanne Hartmann from the Humboldt University Berlin reported on antiinflammatoryhelminth products, e.g. cystatin and tropomyosin, as a basis for drug design.Redox enzymes and polyamines were the topic of the fourth session. Andreas Kraskyfrom Akzo Nobel Intervet Innovation GmbH at Schwabenheim reported on virtual highthrouphputscreening for structure-based drug design based on the example of flavonedisulfideoxido-reductases from different parasites, like trypanosomatids and Plasmodium. Ina series of four talks the results obtained in the laboratory of Prof. Katja Becker from theJustus-Liebig University Giessen were reported. Christine Nickel spoke about a newperoxiredoxin or antioxidant protein (AOP) from Plasmodium falciparum showing that it was aglutaredoxin-dependent peroxidase detoxifying lipid hydroperoxides. Monique Akoacherepresented her data on glyoxalases from Plasmodium falciparum, showed inhibition in thenanomolar range, and thus underlined the suitability of the glyoxalase system fordevelopment of antimalarial drugs. Marcel Deponte described the classification ofglutaredoxin-like proteins and peroxiredoxins from Sporozoa. Finally, Dr. Stefan Rahlfsspoke about selenoproteins from Plasmodium as potential drug targets. The search forselenocysteine insertion sequences (SECIS) in the genome of Plasmodium falciparumresulted in the identification of four selenoproteins which are specific to Plasmodium. IngridMüller from the BNI presented her studies on arginase from Plasmodium falciparum,demonstrating that this enzyme is manganese-dependent and thus differs significantly fromits mammalian counterparts. Dr. Kai Lüersen from the BNI reported on the polyaminemetabolism in Plasmodium falciparum, and 3-aminooxy-1-aminopropan (APA) as a leadcompound against ornithine decarboxylase was discussed. Moreover, he showed 4-methylcyclohexylamine (4MCHA) as an inhibitor of spermidine synthase. Both inhibitors wereeffective in the micromolar range. Dr. Elisabeth Davioud-Charvet from the BiochemistryCentre at the University of Heidelberg reported on a fluoro-analogue of the menadione-
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