Antimicrobial, Hemolytic, and Cytotoxic Activities of β‐Peptoid–Peptide Hybrid Oligomers: Improved Properties Compared to Natural AMPs

Olsen, Christian A.; Ziegler, Hanne L.; Nielsen, Hanne Mørck; Frimodt‐Møller, Niels; Jaroszewski, Jerzy W.; Franzyk, Henrik

doi:10.1002/cbic.201000232

Cited by 82 publications

(121 citation statements)

References 45 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…Stable peptidomimetics belonging to the class of ␣-peptide/␤-peptoid hybrids, displaying a design with alternating cationic ␣-amino acids and lipophilic peptoid residues, have been shown to imitate the biological effects of natural antimicrobial peptides (e.g. antimicrobial activity, antibiofilm activity, and immunomodulatory activity) (17)(18)(19)(20)(21). We have previously identified a novel class of FPR2 antagonists by screening an array of peptidomimetics comprising several subclasses of ␣-peptide/␤-peptoid hybrids (see Fig.…”

mentioning

confidence: 99%

The Lipidated Peptidomimetic Lau-((S)-Aoc)-(Lys-βNphe)6-NH2 Is a Novel Formyl Peptide Receptor 2 Agonist That Activates Both Human and Mouse Neutrophil NADPH Oxidase

Holdfeldt

Skovbakke

Winther

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Neutrophils expressing formyl peptide receptor 2 (FPR2) play key roles in host defense, immune regulation, and resolution of inflammation. Consequently, the search for FPR2-specific modulators has attracted much attention due to its therapeutic potential. Earlier described agonists for this receptor display potent activity for the human receptor (FPR2) but low activity for the mouse receptor orthologue (Fpr2), rendering them inapplicable in murine models of human disease. Here we describe a novel FPR2 agonist, the proteolytically stable ␣-peptide/␤-pep- The molecular basis for directional neutrophil migration toward inflammatory sites is their ability to sense "danger signals" produced by microorganisms (i.e. pathogen-associated molecular patterns) and damaged host cells or tissues (i.e. damage-associated molecular patterns) (1). Human neutrophils express two members of the formyl peptide receptor family (FPR1 3 and FPR2), belonging to the family of G-protein-coupled receptors (GPCRs), which recognize pathogen-associated molecular patterns in the form of peptides with an N-terminal formyl-methionine residue, originating from bacterial (and mitochondrial) protein synthesis (2, 3). In addition, human neutrophils express GPCRs that recognize endogenous chemoattractants and damage-associated molecular patterns, including the split product of complement component C5 (C5a, recognized by C5aR), leukotriene LTB 4 (recognized by BLT1), the chemokine IL-8 (CXCL8, recognized by CXCR1 and CXCR2), platelet-activating factor (PAF, recognized by PAFR), and the nucleotide ATP (recognized by P2Y 2 R) (4, 5). Although the two human neutrophil FPRs, FPR1 and FPR2, display significant sequence similarity, they have distinct, albeit partially overlapping, ligand recognition profiles (2, 6, 7).The mouse genome contains at least eight mouse Fprs, among which Fpr1 and Fpr2 are regarded as the orthologues of the receptors expressed in human neutrophils (8, 9). Studies using mice deficient in Fpr1 or Fpr2 have demonstrated roles of these receptors not only in host defense but also in immune regulation and in the resolution of inflammation (10 -12). The therapeutic potential of targeting these receptors in inflammatory/infectious conditions, such as atherosclerosis, cancer, neurodegenerative diseases, and sepsis (see a recent review (13)), justifies the search for receptor-specific ligands that can function as agonists, antagonists, or allosteric modulators. However, a direct translation of knowledge between humans and

show abstract

mentioning

confidence: 99%

The Lipidated Peptidomimetic Lau-((S)-Aoc)-(Lys-βNphe)6-NH2 Is a Novel Formyl Peptide Receptor 2 Agonist That Activates Both Human and Mouse Neutrophil NADPH Oxidase

Holdfeldt

Skovbakke

Winther

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The names, sequences, hydrophobicities, antibacterial activities against Gram-negative (E. coli) and Gram-positive (B. subtilis) bacteria, and hemolytic activities of these nine compounds are shown in Table 1 (values in g/ml are provided in Table S1 in the supplemental material). The antibacterial activities are reported as MICs and were determined according to standard CLSI M7-A6 protocols (6); hemolytic activities, determined as previously reported (5), serve as a measure of antimicrobial peptide/peptoid toxicity (9), which is commonly used to optimize antimicrobial peptide/peptoid therapeutic performance (4,5,17,19,(22)(23)(24).…”

mentioning

confidence: 99%

Functional Synergy between Antimicrobial Peptoids and Peptides against Gram-Negative Bacteria

Chongsiriwatana

Wetzler

Barron

2011

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) are integral components of innate immunity and are typically found in combinations in which they can synergize for broader-spectrum or more potent activity. Previously, we reported peptoid mimics of AMPs with potent and selective antimicrobial activity. Using checkerboard assays, we demonstrate that peptoids and AMPs can interact synergistically, with fractional inhibitory concentration indices as low as 0.16. These results strongly suggest that antimicrobial peptoids and peptides are functionally and mechanistically analogous.

show abstract

“…To circumvent those drawbacks, over last decade, non-natural peptidomimetics that mimic the globally amphipathic structures and mechanism of action of HDPs have been developed and investigated, such as β-peptides [17][18][19], peptoids [20][21][22][23][24], arylamide oligomers [25,26], β-turn mimetics [27,28] and others [29,30]. Recently, we developed a new class of peptidomimetics termed 'γ-AApeptides' [31,32].…”

mentioning

confidence: 99%

The Development of Antimicrobial γ-Aapeptides

et al. 2016

View full text Add to dashboard Cite

Host-defense peptides (HDPs) are promising next generation of antibiotic agents, as they have the potential to circumvent emerging drug resistance, due to their mechanism of bacterial killing through disruption of their membranes. Nonetheless, HDPs have intrinsic drawbacks such as low-to-moderate activity, susceptibility to enzymatic degradation. In the past few years, we developed a new class of peptidomimetics named ‘γ-AApeptides’, which have superior resistance to proteolysis and a variety of diversification via straightforward synthesis. Our recent studies suggested that γ-AApeptides can mimic the bactericidal mechanism of HDPs and show potent and broad-spectrum activity against both Gram-positive and Gram-negative multidrug-resistant bacteria. In this review, we summarize our current studies of antimicrobial γ-AApeptides and discuss their potential future development as antimicrobial peptidomimetics.

show abstract

Antimicrobial, Hemolytic, and Cytotoxic Activities of β‐Peptoid–Peptide Hybrid Oligomers: Improved Properties Compared to Natural AMPs

Cited by 82 publications

References 45 publications

The Lipidated Peptidomimetic Lau-((S)-Aoc)-(Lys-βNphe)6-NH2 Is a Novel Formyl Peptide Receptor 2 Agonist That Activates Both Human and Mouse Neutrophil NADPH Oxidase

The Lipidated Peptidomimetic Lau-((S)-Aoc)-(Lys-βNphe)6-NH2 Is a Novel Formyl Peptide Receptor 2 Agonist That Activates Both Human and Mouse Neutrophil NADPH Oxidase

Functional Synergy between Antimicrobial Peptoids and Peptides against Gram-Negative Bacteria

The Development of Antimicrobial γ-Aapeptides

Contact Info

Product

Resources

About