A polypeptide inhibitor of calcineurin blocks the calcineurin-NFAT signalling pathway in vivo and in vitro

Journal of Enzyme Inhibition and Medicinal Chemistry

Yanxia Yin¹  Wenying Li¹  Yuchen Zhang¹  Li Tong¹  Jing Luo¹  Yumeng Yang¹  Ping Wang¹  Na Cheng¹  Nan Zhang¹  Zhimei Li² 

[1] Department of Biochemistry and Molecular Biology, Gene Engineering and Biotechnology of Beijing Key Laboratory, College of Life Sciences, Beijing Normal University;Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases;

关键词: calcineurin;    nfat;    enzyme inhibitor;    polypeptide;   

DOI  :  10.1080/14756366.2021.1998024

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown