A Fluorescence-Polarization-Based Lipopolysaccharide-Caspase-4 Interaction Assay for the Development of Inhibitors.
caspase activation and recruitment domain (CARD)
caspase-4
fluorescence polarization
high-throughput screening
lipopolysaccharides
non-canonical inflammasome
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
11 Apr 2022
11 Apr 2022
Historique:
received:
13
03
2022
revised:
08
04
2022
accepted:
09
04
2022
entrez:
23
4
2022
pubmed:
24
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
Recognition of intracellular lipopolysaccharide (LPS) by Caspase-4 (Casp-4) is critical for host defense against Gram-negative pathogens. LPS binds to the N-terminal caspase activation and recruitment domain (CARD) of procaspase-4, leading to auto-proteolytic activation followed by pro-inflammatory cytokine release and pyroptotic cell death. Aberrant hyper-activation of Casp-4 leads to amplification of the inflammatory response linked to sepsis. While the active site of a caspase has been targeted with peptide inhibitors, inhibition of LPS-Casp-4 interaction is an emerging strategy for the development of selective inhibitors with a new mode of action for treating infectious diseases and sepsis induced by LPS. In this study, a high-throughput screening (HTS) system based on fluorescence polarization (FP) was devised to identify inhibitors of the LPS and Casp-4 interaction. Using HTS and IC
Identifiants
pubmed: 35458656
pii: molecules27082458
doi: 10.3390/molecules27082458
pmc: PMC9032125
pii:
doi:
Substances chimiques
Caspase Inhibitors
0
Inflammasomes
0
Lipopolysaccharides
0
CASP4 protein, human
EC 3.4.22.-
Caspases
EC 3.4.22.-
Caspases, Initiator
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Korea Health Industry Development Institute
ID : HV20C0007
Pays : Republic of Korea
Organisme : National Research Foundation of Korea
ID : 2020R1A2C2100669
Organisme : Korea Institute of Science and Technology
ID : KIST intramural grants
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