Design and Evaluation of Antimalarial Peptides Derived from Prediction of Short Linear Motifs in Proteins Related to Erythrocyte Invasion
| Autor: | Ilias Stavropoulos, Nathalie Doolan, Catherine Mooney, Denis C. Shields, Angus Bell, Alessandra Bianchin, Darren B. Leneghan, Anthony J. Chubb |
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| Přispěvatelé: | Melcher, Ulrich |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Plasmodium
Erythrocytes Amino Acid Motifs Molecular Sequence Data Plasmodium falciparum Protozoan Proteins lcsh:Medicine Peptide Biology Red blood cells Protein–protein interaction Antimalarials Membrane proteins Humans Amino Acid Sequence Malaria Falciparum lcsh:Science Peptide sequence chemistry.chemical_classification Multidisciplinary Merozoites lcsh:R biology.organism_classification Parasitic diseases Transmembrane protein 3. Good health Amino acid Malaria Biochemistry chemistry Membrane protein Drug Design Sequence motif analysis Proteome lcsh:Q Peptides Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 6, p e0127383 (2015) |
| Popis: | 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. Irish Research Council Science Foundation Ireland |
| Databáze: | OpenAIRE |
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