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Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation

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dc.contributor.author Uppu, Divakara S. S. M.
dc.contributor.author Haldar, Jayanta
dc.date.accessioned 2017-01-24T09:11:14Z
dc.date.available 2017-01-24T09:11:14Z
dc.date.issued 2016
dc.identifier.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 en_US
dc.identifier.citation Biomacromolecules en_US
dc.identifier.citation 17 en_US
dc.identifier.citation 3 en_US
dc.identifier.issn 1525-7797
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/2304
dc.description Restricted Access en_US
dc.description.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. en_US
dc.description.uri 1526-4602 en_US
dc.description.uri http://dx.doi.org/10.1021/acs.biomac.5b01567 en_US
dc.language.iso English en_US
dc.publisher American Chemical Society en_US
dc.rights @American Chemical Society, 2016 en_US
dc.subject Biochemistry & Molecular Biology en_US
dc.subject Chemistry en_US
dc.subject Polymer Science en_US
dc.subject Host-Defense Peptides en_US
dc.subject Innate Immune-Response en_US
dc.subject Antimicrobial Peptides en_US
dc.subject Biophysical Characterization en_US
dc.subject Resistant Bacteria en_US
dc.subject Binding-Protein en_US
dc.subject Positive Charge en_US
dc.subject Antibacterial en_US
dc.subject Mimics en_US
dc.subject Sepsis en_US
dc.title Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation en_US
dc.type Article en_US


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