Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2304
Title: Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation
Authors: Uppu, Divakara S. S. M.
Haldar, Jayanta
Keywords: Biochemistry & Molecular Biology
Chemistry
Polymer Science
Host-Defense Peptides
Innate Immune-Response
Antimicrobial Peptides
Biophysical Characterization
Resistant Bacteria
Binding-Protein
Positive Charge
Antibacterial
Mimics
Sepsis
Issue Date: 2016
Publisher: American Chemical Society
Citation: Uppu, Dssm; Haldar, J., Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation. Biomacromolecules 2016, 17 (3), 862-873 http://dx.doi.org/10.1021/acs.biomac.5b01567
Biomacromolecules
17
3
Abstract: Synthetic polymers incorporating the cationic charge and hydrophobicity to mimic the function of antimicrobial peptides (AMPs) have been developed. These cationic-amphiphilic polymers bind to bacterial membranes that generally contain negatively charged phospholipids and cause membrane disintegration resulting in cell death; however, cationic-amphiphilic antibacterial polymers with endotoxin neutralization properties, to the best of our knowledge, have not been reported. Bacterial endotoxins such as lipopolysaccharide (LPS) cause sepsis that is responsible for a great amount of mortality worldwide. These cationic-amphiphilic polymers can also bind to negatively charged and hydrophobic LPS and cause detoxification. Hence, we envisaged that cationic-amphiphilic polymers can have both antibacterial as well as LPS binding properties. Here we report synthetic amphiphilic polymers with both antibacterial as well as endotoxin neutralizing properties. Levels of proinflammatory cytokines in human monocytes caused by LPS stimulation were inhibited by >80% when coincubated with these polymers. These reductions were found to be dependent on concentration and, more importantly, on the side-chain chemical structure due to variations in the hydrophobicity profiles of these polymers. These cationic-amphiphilic polymers bind and cause LPS neutralization and detoxification. Investigations of polymer interaction with LPS using fluorescence spectroscopy and dynamic light scattering (DLS) showed that these polymers bind but neither dissociate nor promote LPS aggregation. We show that polymer binding to LPS leads to sort of a pseudoaggregate formation resulting in LPS neutralization/detoxification. These findings provide an unusual mechanism of LPS neutralization using novel synthetic cationic-amphiphilic polymers.
Description: Restricted Access
URI: http://hdl.handle.net/10572/2304
ISSN: 1525-7797
Appears in Collections:Research Papers (Jayanta Haldar)

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