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.

Villa, S., Legnani, L., Colombo, D., Gelain, A., Lammi, C., Bongiorno, D., et al. (2018). Structure-based drug design, synthesis and biological assays of P. falciparum Atg3–Atg8 protein–protein interaction inhibitors. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 32(3), 473-486 [10.1007/s10822-018-0102-5].

Structure-based drug design, synthesis and biological assays of P. falciparum Atg3–Atg8 protein–protein interaction inhibitors

Laura Legnani;
2018

Abstract

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.
Articolo in rivista - Articolo scientifico
1,2,3-Triazole; Atg8 inhibitors; Autophagy; Docking; Malaria; Peptidomimetics; PPI inhibitors;
English
473
486
14
Villa, S., Legnani, L., Colombo, D., Gelain, A., Lammi, C., Bongiorno, D., et al. (2018). Structure-based drug design, synthesis and biological assays of P. falciparum Atg3–Atg8 protein–protein interaction inhibitors. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 32(3), 473-486 [10.1007/s10822-018-0102-5].
Villa, S; Legnani, L; Colombo, D; Gelain, A; Lammi, C; Bongiorno, D; Ilboudo, D; Mcgee, K; Bosch, J; Grazioso, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/351981
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