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Novel African Trypanocidal Agents: Membrane Rigidifying Peptides
The bloodstream developmental forms of pathogenic African trypanosomes are uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal activity is conferred by peptide hydrophobicity and charge distribution and results from increased rigidity of the plasma membrane. Structural analys...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436892/ https://www.ncbi.nlm.nih.gov/pubmed/22970207 http://dx.doi.org/10.1371/journal.pone.0044384 |
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author | Harrington, John M. Scelsi, Chris Hartel, Andreas Jones, Nicola G. Engstler, Markus Capewell, Paul MacLeod, Annette Hajduk, Stephen |
author_facet | Harrington, John M. Scelsi, Chris Hartel, Andreas Jones, Nicola G. Engstler, Markus Capewell, Paul MacLeod, Annette Hajduk, Stephen |
author_sort | Harrington, John M. |
collection | PubMed |
description | The bloodstream developmental forms of pathogenic African trypanosomes are uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal activity is conferred by peptide hydrophobicity and charge distribution and results from increased rigidity of the plasma membrane. Structural analysis of lipid-associated peptide suggests a mechanism of phospholipid clamping in which an internal hydrophobic bulge anchors the peptide in the membrane and positively charged moieties at the termini coordinate phosphates of the polar lipid headgroups. This mechanism reveals a necessary phenotype in bloodstream form African trypanosomes, high membrane fluidity, and we suggest that targeting the plasma membrane lipid bilayer as a whole may be a novel strategy for the development of new pharmaceutical agents. Additionally, the peptides we have described may be valuable tools for probing the biosynthetic machinery responsible for the unique composition and characteristics of African trypanosome plasma membranes. |
format | Online Article Text |
id | pubmed-3436892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34368922012-09-11 Novel African Trypanocidal Agents: Membrane Rigidifying Peptides Harrington, John M. Scelsi, Chris Hartel, Andreas Jones, Nicola G. Engstler, Markus Capewell, Paul MacLeod, Annette Hajduk, Stephen PLoS One Research Article The bloodstream developmental forms of pathogenic African trypanosomes are uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal activity is conferred by peptide hydrophobicity and charge distribution and results from increased rigidity of the plasma membrane. Structural analysis of lipid-associated peptide suggests a mechanism of phospholipid clamping in which an internal hydrophobic bulge anchors the peptide in the membrane and positively charged moieties at the termini coordinate phosphates of the polar lipid headgroups. This mechanism reveals a necessary phenotype in bloodstream form African trypanosomes, high membrane fluidity, and we suggest that targeting the plasma membrane lipid bilayer as a whole may be a novel strategy for the development of new pharmaceutical agents. Additionally, the peptides we have described may be valuable tools for probing the biosynthetic machinery responsible for the unique composition and characteristics of African trypanosome plasma membranes. Public Library of Science 2012-09-07 /pmc/articles/PMC3436892/ /pubmed/22970207 http://dx.doi.org/10.1371/journal.pone.0044384 Text en © 2012 Harrington et al http://creativecommons.org/licenses/by/4.0/ This 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 properly credited. |
spellingShingle | Research Article Harrington, John M. Scelsi, Chris Hartel, Andreas Jones, Nicola G. Engstler, Markus Capewell, Paul MacLeod, Annette Hajduk, Stephen Novel African Trypanocidal Agents: Membrane Rigidifying Peptides |
title | Novel African Trypanocidal Agents: Membrane Rigidifying Peptides |
title_full | Novel African Trypanocidal Agents: Membrane Rigidifying Peptides |
title_fullStr | Novel African Trypanocidal Agents: Membrane Rigidifying Peptides |
title_full_unstemmed | Novel African Trypanocidal Agents: Membrane Rigidifying Peptides |
title_short | Novel African Trypanocidal Agents: Membrane Rigidifying Peptides |
title_sort | novel african trypanocidal agents: membrane rigidifying peptides |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436892/ https://www.ncbi.nlm.nih.gov/pubmed/22970207 http://dx.doi.org/10.1371/journal.pone.0044384 |
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