Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects
(2017) In Scientific Reports 7(1).- Abstract
The objective of the present study is the investigation of possibilities for boosting peptide antiinflammatory 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... (More)
The objective of the present study is the investigation of possibilities for boosting peptide antiinflammatory 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.
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- author
- Singh, Shalini ; Datta, Aritreyee ; Schmidtchen, Artur LU ; Bhunia, Anirban and Malmsten, Martin LU
- organization
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 7
- issue
- 1
- article number
- 212
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:28303012
- scopus:85031323437
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-017-00188-7
- language
- English
- LU publication?
- yes
- id
- 4a4f4a54-7298-406c-906f-c947cea69aad
- date added to LUP
- 2017-10-30 09:22:48
- date last changed
- 2024-03-01 00:51:51
@article{4a4f4a54-7298-406c-906f-c947cea69aad,
abstract = {{<p>The objective of the present study is the investigation of possibilities for boosting peptide antiinflammatory 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.</p>}},
author = {{Singh, Shalini and Datta, Aritreyee and Schmidtchen, Artur and Bhunia, Anirban and Malmsten, Martin}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Tryptophan end-tagging for promoted lipopolysaccharide interactions and anti-inflammatory effects}},
url = {{http://dx.doi.org/10.1038/s41598-017-00188-7}},
doi = {{10.1038/s41598-017-00188-7}},
volume = {{7}},
year = {{2017}},
}