Department of Biochemistry and Molecular Biology, Gene Engineering and Biotechnology of Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, China.
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing, China.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):202-210. doi: 10.1080/14756366.2021.1998024.
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.
钙调磷酸酶（CN）通过调节活化 T 细胞核因子（NFAT）来控制免疫反应。抑制 CN 的功能是治疗免疫疾病的有效方法。PVIVIT 肽是一种基于 NFAT-PxIxIT 基序的人工肽，与 CN 具有更强的结合能力。设计了一种抑制 CN/NFAT 相互作用的生物活性肽（命名为 pep4）。Pep4 包含 A238L 作为接头和 LxVP 基序和 PVIVIT 基序作为 CN 结合位点。Pep4 与 CN 具有很强的结合能力，并竞争性抑制 CN 活性。11-精氨酸修饰的 pep4（11R-pep4）抑制 NFAT 的核易位并降低 IL-2 的表达。11R-pep4 在一定程度上改善了哮喘小鼠的病理特征。上述结果表明 pep4 是一种高亲和力的 CN 抑制剂。这些发现将有助于发现新的 CN 抑制剂和有前途的免疫抑制剂。
