Novel African trypanocidal agents: membrane rigidifying peptides

Harrington, J.M., Scelsi, C., Hartel, A., Jones, N.G., Engstler, M., Capewell, P. , MacLeod, A. and Hajduk, S. (2012) Novel African trypanocidal agents: membrane rigidifying peptides. PLoS ONE, 7(9), e44384. (doi:10.1371/journal.pone.0044384) (PMID:22970207) (PMCID:PMC3436892)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLeod, Professor Annette and Capewell, Dr Paul
Authors: Harrington, J.M., Scelsi, C., Hartel, A., Jones, N.G., Engstler, M., Capewell, P., MacLeod, A., and Hajduk, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PLoS ONE 7(9):e44384
Publisher Policy:Reproduced under a Creative Commons License

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