Bianchin, AlessandraAlessandraBianchinBell, AngusAngusBellChubb, Anthony J.Anthony J.ChubbDoolan, NathalieNathalieDoolanLeneghan, DarrenDarrenLeneghanStavropoulos, IliasIliasStavropoulosShields, Denis C.Denis C.ShieldsMooney, CatherineCatherineMooneyMelcher, Ulrich2019-04-232019-04-232015 the A2015-06-03PLoS ONE1932-6203http://hdl.handle.net/10197/10069The purpose of this study was to investigate the blood stage of the malaria causing parasite, Plasmodium falciparum, to predict potential protein interactions between the parasite merozoite and the host erythrocyte and design peptides that could interrupt these predicted interactions. We screened the P. falciparum and human proteomes for computationally predicted short linear motifs (SLiMs) in cytoplasmic portions of transmembrane proteins that could play roles in the invasion of the erythrocyte by the merozoite, an essential step in malarial pathogenesis. We tested thirteen peptides predicted to contain SLiMs, twelve of them palmitoylated to enhance membrane targeting, and found three that blocked parasite growth in culture by inhibiting the initiation of new infections in erythrocytes. Scrambled peptides for two of the most promising peptides suggested that their activity may be reflective of amino acid properties, in particular, positive charge. However, one peptide showed effects which were stronger than those of scrambled peptides. This was derived from human red blood cell glycophorin-B. We concluded that proteome-wide computational screening of the intracellular regions of both host and pathogen adhesion proteins provides potential lead peptides for the development of anti-malarial compounds.Electronic-eCollectionenThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedRed blood cellsMerozoitesPlasmodiumParasitic diseasesSequence motif analysisMembrane proteinsMalariaAntimalarialsJournal Article106e012738310.1371/journal.pone.01273832018-07-2108/IN.1/B186410/RFP/GEN2749https://creativecommons.org/licenses/by-nc-nd/3.0/ie/