Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity

Research output: Contribution to journalJournal articleResearchpeer-review

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Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity. / Skovbakke, Sarah Line; Larsen, Camilla Josephine; Heegaard, Peter Mikael Helweg; Moesby, Lise; Franzyk, Henrik.

In: Journal of Medicinal Chemistry, Vol. 58, No. 2, 2015, p. 801-813.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Skovbakke, SL, Larsen, CJ, Heegaard, PMH, Moesby, L & Franzyk, H 2015, 'Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity' Journal of Medicinal Chemistry, vol. 58, no. 2, pp. 801-813. https://doi.org/10.1021/jm501341h

APA

Skovbakke, S. L., Larsen, C. J., Heegaard, P. M. H., Moesby, L., & Franzyk, H. (2015). Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity. Journal of Medicinal Chemistry, 58(2), 801-813. https://doi.org/10.1021/jm501341h

Vancouver

Skovbakke SL, Larsen CJ, Heegaard PMH, Moesby L, Franzyk H. Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity. Journal of Medicinal Chemistry. 2015;58(2):801-813. https://doi.org/10.1021/jm501341h

Author

Skovbakke, Sarah Line ; Larsen, Camilla Josephine ; Heegaard, Peter Mikael Helweg ; Moesby, Lise ; Franzyk, Henrik. / Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity. In: Journal of Medicinal Chemistry. 2015 ; Vol. 58, No. 2. pp. 801-813.

Bibtex

@article{4e2a2f15b8094623b85ff48bdd52fded,
title = "Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity",
abstract = "In this study we investigated, optimized, and characterized a novel subclass of host defense peptide (HDP) mimics based on α-peptide/β-peptoid hybrid oligomers with an alternating cationic/hydrophobic design with respect to their ability to modulate the pro-inflammatory response by human primary leukocytes upon exposure to bacterial components. Structure-activity studies revealed that certain lipidated α-peptide/β-peptoid hybrid oligomers possess anti-inflammatory activities in the submicromolar range with low cytotoxicity, and that the anti-inflammatory activity of the HDP mimics is dependent on the length and position of the lipid element(s). The resulting lead compound, Pam-(Lys-βNSpe)6-NH2, blocks LPS-induced cytokine secretion with a potency comparable to that of polymyxin B. The mode of action of this HDP mimic does not involve direct LPS interaction since it, in contrast to polymyxin B, displayed only minor activity in the Limulus amebocyte lysate assay. Flow cytometry data showed specific interaction of a fluorophore-labeled lipidated α-peptide/β-peptoid hybrid with monocytes and granulocytes indicating a cellular target expressed by these leukocyte subsets.",
author = "Skovbakke, {Sarah Line} and Larsen, {Camilla Josephine} and Heegaard, {Peter Mikael Helweg} and Lise Moesby and Henrik Franzyk",
year = "2015",
doi = "10.1021/jm501341h",
language = "English",
volume = "58",
pages = "801--813",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "2",

}

RIS

TY - JOUR

T1 - Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity

AU - Skovbakke, Sarah Line

AU - Larsen, Camilla Josephine

AU - Heegaard, Peter Mikael Helweg

AU - Moesby, Lise

AU - Franzyk, Henrik

PY - 2015

Y1 - 2015

N2 - In this study we investigated, optimized, and characterized a novel subclass of host defense peptide (HDP) mimics based on α-peptide/β-peptoid hybrid oligomers with an alternating cationic/hydrophobic design with respect to their ability to modulate the pro-inflammatory response by human primary leukocytes upon exposure to bacterial components. Structure-activity studies revealed that certain lipidated α-peptide/β-peptoid hybrid oligomers possess anti-inflammatory activities in the submicromolar range with low cytotoxicity, and that the anti-inflammatory activity of the HDP mimics is dependent on the length and position of the lipid element(s). The resulting lead compound, Pam-(Lys-βNSpe)6-NH2, blocks LPS-induced cytokine secretion with a potency comparable to that of polymyxin B. The mode of action of this HDP mimic does not involve direct LPS interaction since it, in contrast to polymyxin B, displayed only minor activity in the Limulus amebocyte lysate assay. Flow cytometry data showed specific interaction of a fluorophore-labeled lipidated α-peptide/β-peptoid hybrid with monocytes and granulocytes indicating a cellular target expressed by these leukocyte subsets.

AB - In this study we investigated, optimized, and characterized a novel subclass of host defense peptide (HDP) mimics based on α-peptide/β-peptoid hybrid oligomers with an alternating cationic/hydrophobic design with respect to their ability to modulate the pro-inflammatory response by human primary leukocytes upon exposure to bacterial components. Structure-activity studies revealed that certain lipidated α-peptide/β-peptoid hybrid oligomers possess anti-inflammatory activities in the submicromolar range with low cytotoxicity, and that the anti-inflammatory activity of the HDP mimics is dependent on the length and position of the lipid element(s). The resulting lead compound, Pam-(Lys-βNSpe)6-NH2, blocks LPS-induced cytokine secretion with a potency comparable to that of polymyxin B. The mode of action of this HDP mimic does not involve direct LPS interaction since it, in contrast to polymyxin B, displayed only minor activity in the Limulus amebocyte lysate assay. Flow cytometry data showed specific interaction of a fluorophore-labeled lipidated α-peptide/β-peptoid hybrid with monocytes and granulocytes indicating a cellular target expressed by these leukocyte subsets.

U2 - 10.1021/jm501341h

DO - 10.1021/jm501341h

M3 - Journal article

VL - 58

SP - 801

EP - 813

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 2

ER -

ID: 129418778