LEISHDRUG Consortium

Collaborative Project



Restricted Area


WP3 is carried out at the Consejo Superior de Investigaciones Científicas (CSIC) in Madrid, and the The Pompeu Fabra University (UPF) in Barcelona. The principal investigators are Dr. Luis Rivas, head of the Antimicrobial Peptide Group of the Center for Biological Research (CIB), and Dr. David Andreu, head of the Proteomics and Protein Chemistry Unit at UPF. WP3 uses dedicated combinatorial peptide libraries with a bias on sequence signatures derived from consortium results (partners 1, 3, 5, 7, 8, 11, [7]) that will be tested on parasites in culture (partner 1) and macrophage infection assays (partner 6). The major aim of this work package is to identify anti-leishmanial peptides that specifically target the Leishmania kinome. We will utilize cell penetrating peptides (CPPs) [46], with or without microbicidal activity [47] optimized for Leishmania to deliver peptides that are recognized by Leishmania kinases, thus competing with the endogenous substrate and interfering with signaling processes relevant for intracellular parasite survival and virulence. Libraries of defined composition will be prepared by parallel solid phase peptide synthesis on either conventional resin beads or cellulose membranes (SPOT synthesis [48]). In both cases, Fmoc/butyl chemistry [49] will be used, which allows incorporation of practically any amino acid, natural or otherwise, including phosphorylated Ser, Thr and Tyr [50]. CPPs are able to deliver a variety of molecules, including drugs and peptides, bypassing limitations associated with receptor-mediated uptake (receptor expression, ligand conformation etc.). Our approach thus opens new therapeutic possibilities, which will be applicable to the lead compounds identified by consortium partners (partners 1, 2, 10).