The proteins involved in the autophagy (Atg) pathway have recently been considered promising targets for the development of new antimalarial drugs. In particular, inhibitors of the protein-protein interaction (PPI) between Atg3 and Atg8 of Plasmodium falciparum retarded the blood- and liver-stages of parasite growth. In this paper, we used computational techniques to design a new class of peptidomimetics mimicking the Atg3 interaction motif, which were then synthesized by click-chemistry. Surface plasmon resonance has been employed to measure the ability of these compounds to inhibit the Atg3-Atg8 reciprocal protein-protein interaction. Moreover, P. falciparum growth inhibition in red blood cell cultures was evaluated as well as the cyto-toxicity of the compounds.
Structure-based drug design, synthesis and biological assays of P. falciparum Atg3-Atg8 protein-protein interaction inhibitors / S. Villa, L. Legnani, D. Colombo, A. Gelain, C. Lammi, D. Bongiorno, D.P. Ilboudo, K.E. Mcgee, J. Bosch, G. Grazioso. - In: JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN. - ISSN 0920-654X. - 32:3(2018 Mar 01), pp. 473-486.
Titolo: | Structure-based drug design, synthesis and biological assays of P. falciparum Atg3-Atg8 protein-protein interaction inhibitors |
Autori: | VILLA, STEFANIA (Primo) LEGNANI, LAURA (Secondo) GRAZIOSO, GIOVANNI (Ultimo) |
Parole Chiave: | 1,2,3-Triazole; Atg8 inhibitors; Autophagy; Docking; Malaria; Peptidomimetics; PPI inhibitors; Drug Discovery3003 Pharmaceutical Science; Computer Science Applications1707 Computer Vision and Pattern Recognition; Physical and Theoretical Chemistry |
Settore Scientifico Disciplinare: | Settore CHIM/08 - Chimica Farmaceutica |
Data di pubblicazione: | 1-mar-2018 |
Rivista: | |
Tipologia: | Article (author) |
Data ahead of print / Data di stampa: | 30-gen-2018 |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1007/s10822-018-0102-5 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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