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<strong>Proceedings</strong> of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Design and Synthesis of Protein-Protein Interaction Mimics asPlasmodium Falciparum Cysteine ProteaseFalcipain-2 InhibitorsLuca Rizzi 1 , Srividhya Sundararaman 2 , Katarina Cendic 1 ,Nadia Vaiana 1 , Reshma Korde 2 , Dipto Sinha 2 , Asif Mohommed 2 ,Pawan Malhotra 2 , and Sergio Romeo 11 Dipartimento di Scienze Farmaceutiche “Pietro Pratesi”, Università degli Studi diMilano, Via L. Mangiagalli 25, 20133, Milan, Italy; 2 International Centre for GeneticEngineering and Biotechnology, Aruna Asaf Ali Marg, NewDelhi, 110067, IndiaIntroductionCysteine proteases play a significant role in the growth and the development of severalhuman parasites such as Plasmodium, Leishmania, and Trypanosoma which affect morethan 3.5 billion people worldwide. Falcipain-2 (FP-2) isan important cysteine protease of the human malariaparasite, P. falciparum (Pf), and is one of the mostpromising targets for the development of new Pfinhibitors [1]. FP-2 plays roles in haemoglobindegradation and merozoites egression at the asexualblood stages of Plasmodium development.Cystatins are endogenous proteinaceous cysteineprotease inhibitors that have been described in anumber of eukaryotic systems, but the high molecularweight and the peptidic structure raise difficulties intheir exploitation in drug design [2]. Small moleculesFig. 1. Interacting domains ofCEWC.mimicking the interaction between FP-2 and Cystatincould be a starting point for the development of a newclass of anti-malarial.Fig. 2. Synthesized peptides and their effect on P. falciparum morphology.238

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