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Study · In vitro (cells) · 2023

1 result

Chimeric Peptidomimetic Antibiotic Efficiently Neutralizes Lipopolysaccharides (LPS) and Bacteria-Induced Activation of RAW Macrophages.

Javed A, Slingerland CJ, Wood TM, Martin NI, Broere F, Weingarth MH, Veldhuizen EJA

ACS infectious diseases15 Feb 2023Cited by 12 (Europe PMC)

PMID36790385 (opens in a new tab)PMCIDPMC10012172 (opens in a new tab)DOI10.1021/acsinfecdis.2c00518 (opens in a new tab)PepBankPUB-36790385
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Summary

Peptide antibiotics have gathered attention given the urgent need to discover antimicrobials with new mechanisms of action. Their extended role as immunomodulators makes them interesting candidates for the development of compounds with dual mode of action. The objective of this study was to test the anti-inflammatory capacity of a recently reported chimeric peptidomimetic antibiotic (CPA) composed of polymyxin B nonapeptide (PMBN) and a macrocyclic β-hairpin motif (MHM). We investigated the potential of CPA to inhibit lipopolysaccharide (LPS)-induced activation of RAW264.7 macrophages. In addition, we elucidated which structural motif was responsible for this activity by testing CPA, its building blocks, and their parent compounds separately. CPA showed excellent LPS neutralizing activity for both smooth and rough LPSs. At nanomolar concentrations, CPA completely inhibited LPS-induced nitric oxide, TNF-α, and IL-10 secretion. Murepavadin, MHM, and PMBN were incapable of neutralizing LPS in this assay, while PMB was less active compared to CPA. Isothermal titration calorimetry showed strong binding between the CPA and LPS with similar binding characteristics also found for the other compounds, indicating that binding does not necessarily correlate with neutralization of LPS. Finally, we showed that CPA-killed bacteria caused significantly less macrophage activation than bacteria killed with gentamicin, heat, or any of the other compounds. This indicates that the combined killing activity and LPS neutralization of CPA can prevent unwanted inflammation, which could be a major advantage over conventional antibiotics. Our data suggests that immunomodulatory activity can further strengthen the therapeutic potential of peptide antibiotics and should be included in the characterization of novel compounds.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

1 result from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Activity measurement

    In a macrophage assay, murepavadin was incapable of neutralizing LPS.

    In plain wordsIn lab tests, murepavadin did not neutralize LPS in a macrophage assay.

    Peptide
    Murepavadin
    Outcome
    No significant changeLPS neutralization
    Study

    n: not reported in source

    RAW264.7 macrophage LPS assay
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Murepavadin, MHM, and PMBN were incapable of neutralizing LPS in this assay
    2 context sentences
    Summary · context
    We investigated the potential of CPA to inhibit lipopolysaccharide (LPS)-induced activation of RAW264.7 macrophages.
    Summary · context
    In addition, we elucidated which structural motif was responsible for this activity by testing CPA, its building blocks, and their parent compounds separately.

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    27 Oct 2026, 18:20 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:32 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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