A polypeptide inhibitor of calcineurin blocks the calcineurin-NFAT signalling pathway in vivo and in vitro.
J Enzyme Inhib Med Chem
; 37(1): 202-210, 2022 Dec.
Article
en En
| MEDLINE
| ID: mdl-34894973
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
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Asma
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Calcineurina
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Factores de Transcripción NFATC
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China