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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 <jats:italic>E. coli<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/s41598-017-00188-7","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T12:08:24Z","timestamp":1489147704000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects"],"prefix":"10.1038","volume":"7","author":[{"given":"Shalini","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aritreyee","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Schmidtchen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-2842","authenticated-orcid":false,"given":"Anirban","family":"Bhunia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Malmsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"188_CR1","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1038\/nbt1267","volume":"24","author":"RE Hancock","year":"2006","unstructured":"Hancock, R. 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