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12:02
An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity
Published on: November 2, 2016
Novel African trypanocidal agents: membrane rigidifying peptides
John M Harrington1, Chris Scelsi, Andreas Hartel
1Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America.
Plos One
|September 13, 2012
Summary
Small hydrophobic peptides kill African trypanosomes by increasing membrane rigidity. This discovery reveals a new drug target and research tool for African trypanosome infections.
Area of Science:
- Parasitology
- Biochemistry
- Membrane Biology
Background:
- Pathogenic African trypanosomes, responsible for sleeping sickness, possess unique bloodstream developmental forms.
- These forms exhibit unusual susceptibility to killing by small hydrophobic peptides.
Purpose of the Study:
- To elucidate the mechanism by which small hydrophobic peptides exert trypanocidal activity.
- To identify novel therapeutic strategies and research tools for African trypanosomiasis.
Main Methods:
- Structural analysis of lipid-associated peptides.
- Investigation of peptide-induced changes in plasma membrane properties.
Main Results:
- Peptide hydrophobicity and charge distribution determine trypanocidal activity.
- A 'phospholipid clamping' mechanism was proposed, involving peptide anchoring and coordination of lipid headgroups.
- This mechanism highlights the essential role of high membrane fluidity in bloodstream form trypanosomes.
Conclusions:
- Targeting the plasma membrane lipid bilayer presents a novel pharmaceutical strategy against African trypanosomes.
- The described peptides can serve as valuable tools for studying trypanosome membrane biosynthesis.
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