Design and Evaluation of Antimalarial Peptides Derived from Prediction of Short Linear Motifs in Proteins Related to Erythrocyte Invasion

Title: Design and Evaluation of Antimalarial Peptides Derived from Prediction of Short Linear Motifs in Proteins Related to Erythrocyte Invasion
Authors: Bianchin, Alessandra
Bell, Angus
Chubb, Anthony J.
Doolan, Nathalie
Leneghan, Darren
Stavropoulos, Ilias
Shields, Denis C.
Mooney, Catherine
Permanent link: http://hdl.handle.net/10197/10069
Date: 3-Jun-2015
Online since: 2019-04-23T09:37:40Z
Abstract: The 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.
Funding Details: Irish Research Council
Science Foundation Ireland
Type of material: Journal Article
Publisher: PLoS
Journal: PLoS ONE
Volume: 10
Issue: 6
Start page: e0127383
Copyright (published version): 2015 the Authors
Keywords: Red blood cellsMerozoitesPlasmodiumParasitic diseasesSequence motif analysisMembrane proteinsMalariaAntimalarials
DOI: 10.1371/journal.pone.0127383
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Computer Science Research Collection

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