Type

Journal Article

Authors

Catherine Mooney
Denis C. Shields
Ilias Stavropoulos
Darren Leneghan
Nathalie Doolan
Anthony J. Chubb
Angus Bell
Alessandra Bianchin

Subjects

Biochemistry

Topics
red blood cell anti malarial peptides short linear motifs amino acid plasmodium falciparum erythrocyte invasion proteins

Design and evaluation of antimalarial peptides derived from prediction of short linear motifs in proteins related to erythrocyte invasion. (2014)

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.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Catherine Mooney, Denis C. Shields, Ilias Stavropoulos, Darren Leneghan, Nathalie Doolan, Anthony J. Chubb, Angus Bell, Alessandra Bianchin

Experts in our system

1
Catherine Mooney
University College Dublin
Total Publications: 63
 
2
Denis C. Shields
University College Dublin
Total Publications: 123
 
3
Darren Leneghan
Trinity College Dublin
Total Publications: 5
 
4
Anthony J Chubb
Royal College of Surgeons in Ireland
Total Publications: 21
 
5
Angus Bell
Trinity College Dublin
Total Publications: 33