Novel African Trypanocidal Agents: Membrane Rigidifying Peptides
Please always quote using this URN: urn:nbn:de:bvb:20-opus-135179
- 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 lipidThe 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.…
Author: | John M. Harrington, Chris Scelsi, Andreas Hartel, Nicola G. Jones, Markus Engstler, Paul Capewell, Annette MacLeod, Stephen Hajduk |
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URN: | urn:nbn:de:bvb:20-opus-135179 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Language: | English |
Parent Title (English): | PLoS One |
Year of Completion: | 2012 |
Volume: | 7 |
Issue: | 9 |
Pagenumber: | e44384 |
Source: | PLoS ONE 7(9): e44384. doi:10.1371/journal.pone.0044384 |
DOI: | https://doi.org/10.1371/journal.pone.0044384 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Tag: | bilayers; binding; brucei; cell surface; depth; environment; probes; protein; signal peptides; trypanosome lytic factor |
Release Date: | 2018/03/23 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |