Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects

Abstract The objective of the present study is the investigation of possibilities for boosting peptide anti-inflammatory effects by tryptophan end-tagging, including identification of underlying mechanisms for this. In doing so, effects of tryptophan end-tagging of KYE21 (KYEITTIHNLFRKLTHRLFRR), a p...

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Autores principales:	Shalini Singh, Aritreyee Datta, Artur Schmidtchen, Anirban Bhunia, Martin Malmsten
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f65c1f8134054b4c90fb6f804fea7fad
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spelling	oai:doaj.org-article:f65c1f8134054b4c90fb6f804fea7fad2021-12-02T16:07:43ZTryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects10.1038/s41598-017-00188-72045-2322https://doaj.org/article/f65c1f8134054b4c90fb6f804fea7fad2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00188-7https://doaj.org/toc/2045-2322Abstract The objective of the present study is the investigation of possibilities for boosting peptide anti-inflammatory effects by tryptophan end-tagging, including identification of underlying mechanisms for this. In doing so, effects of tryptophan end-tagging of KYE21 (KYEITTIHNLFRKLTHRLFRR), a peptide derived from heparin co-factor II, on membrane and lipopolysaccharide (LPS) interactions were investigated by ellipsometry, NMR, fluorescence spectroscopy, and circular dichroism measurements. Through its N-terminal W stretch, WWWKYE21 displays higher membrane binding, liposome rupture, and bacterial killing than unmodified KYE21. Analogously, W-tagging promotes binding to E. coli LPS and to its endotoxic lipid A moiety. Furthermore, WWWKYE21 causes more stable peptide/LPS complexes than KYE21, as evidenced by detailed NMR studies, adopting a pronounced helical conformation, with a large hydrophobic surface at the N-terminus due to the presence of W-residues, and a flexible C-terminus due to presence of several positively charged arginine residues. Mirroring its increased affinity for LPS and lipid A, WWWKYE21 displays strongly increased anti-inflammatory effect due to a combination of direct lipid A binding, peptide-induced charge reversal of cell membranes for LPS scavenging, and peptide-induced fragmentation of LPS aggregates for improved phagocytosis. Importantly, potent anti-inflammatory effects were observed at low cell toxicity, demonstrated for both monocytes and erythrocytes.Shalini SinghAritreyee DattaArtur SchmidtchenAnirban BhuniaMartin MalmstenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shalini Singh Aritreyee Datta Artur Schmidtchen Anirban Bhunia Martin Malmsten Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
description	Abstract The objective of the present study is the investigation of possibilities for boosting peptide anti-inflammatory effects by tryptophan end-tagging, including identification of underlying mechanisms for this. In doing so, effects of tryptophan end-tagging of KYE21 (KYEITTIHNLFRKLTHRLFRR), a peptide derived from heparin co-factor II, on membrane and lipopolysaccharide (LPS) interactions were investigated by ellipsometry, NMR, fluorescence spectroscopy, and circular dichroism measurements. Through its N-terminal W stretch, WWWKYE21 displays higher membrane binding, liposome rupture, and bacterial killing than unmodified KYE21. Analogously, W-tagging promotes binding to E. coli LPS and to its endotoxic lipid A moiety. Furthermore, WWWKYE21 causes more stable peptide/LPS complexes than KYE21, as evidenced by detailed NMR studies, adopting a pronounced helical conformation, with a large hydrophobic surface at the N-terminus due to the presence of W-residues, and a flexible C-terminus due to presence of several positively charged arginine residues. Mirroring its increased affinity for LPS and lipid A, WWWKYE21 displays strongly increased anti-inflammatory effect due to a combination of direct lipid A binding, peptide-induced charge reversal of cell membranes for LPS scavenging, and peptide-induced fragmentation of LPS aggregates for improved phagocytosis. Importantly, potent anti-inflammatory effects were observed at low cell toxicity, demonstrated for both monocytes and erythrocytes.
format	article
author	Shalini Singh Aritreyee Datta Artur Schmidtchen Anirban Bhunia Martin Malmsten
author_facet	Shalini Singh Aritreyee Datta Artur Schmidtchen Anirban Bhunia Martin Malmsten
author_sort	Shalini Singh
title	Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
title_short	Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
title_full	Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
title_fullStr	Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
title_full_unstemmed	Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
title_sort	tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f65c1f8134054b4c90fb6f804fea7fad
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Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects

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