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

Related Articles

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

J Comput Aided Mol Des. 2018 Jan 30;:

Authors: Villa S, Legnani L, Colombo D, Gelain A, Lammi C, Bongiorno D, Ilboudo DP, McGee KE, Bosch J, Grazioso G

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.

PMID: 29383466 [PubMed - as supplied by publisher]

from #PM All via ola Kala on Inoreader http://ift.tt/2FzENX3