A polypeptide inhibitor of calcineurin blocks the calcineurin-NFAT signalling pathway
Animals
Asthma
/ drug therapy
Calcineurin
/ metabolism
Cells, Cultured
Disease Models, Animal
Dose-Response Relationship, Drug
HEK293 Cells
Humans
Male
Mice
Mice, Inbred BALB C
Molecular Structure
NFATC Transcription Factors
/ antagonists & inhibitors
Peptides
/ chemical synthesis
Signal Transduction
/ drug effects
Structure-Activity Relationship
Calcineurin
NFAT
enzyme inhibitor
polypeptide
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
entrez:
13
12
2021
pubmed:
14
12
2021
medline:
24
2
2022
Statut:
ppublish
Résumé
Calcineurin (CN) controls the immune response by regulating nuclear factor of activated T cells (NFAT). Inhibition of CN function is an effective treatment for immune diseases. The PVIVIT peptide is an artificial peptide based on the NFAT-PxIxIT motif, which exhibits stronger binding to CN. A bioactive peptide (named pep4) that inhibits the CN/NFAT interaction was designed. Pep4 contains a segment of A238L as the linker and the LxVP motif and PVIVIT motif as CN binding sites. Pep4 has strong binding capacity to CN and inhibits CN activity competitively. 11-arginine-modified pep4 (11 R-pep4) inhibits the nuclear translocation of NFAT and reduces the expression of IL-2. 11 R-pep4 improves the pathological characteristics of asthmatic mice to a certain extent. The above results indicated that pep4 is a high-affinity CN inhibitor. These findings will contribute to the discovery of new CN inhibitors and promising immunosuppressive drugs.
Identifiants
pubmed: 34894973
doi: 10.1080/14756366.2021.1998024
pmc: PMC8667882
doi:
Substances chimiques
NFATC Transcription Factors
0
Peptides
0
Calcineurin
EC 3.1.3.16
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
202-210Références
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