SLF

FK-506是一种强效免疫抑制剂，与FK-506结合蛋白12（FKBP12）形成高亲和力复合物（Ki=0.2nM）。这种复合物抑制钙/钙调蛋白依赖性蛋白磷酸酶，即钙调磷酸酶的活性，导致T细胞激活的破坏。SLF是一种细胞通透性FK-506类似物，与FKBP紧密结合但缺乏抑制钙调磷酸酶的能力。单独的SLF不表现出显著的细胞反应。然而，SLF的同源二聚体或与另一种蛋白配体的异源二聚体，提供了一种促进配体特异性融合蛋白二聚化以在细胞环境中诱导信号事件的方法。例如，通过10个原子的连接子连接的SLF单体通过Fas-FKBP融合蛋白激活Fas信号，EC50为6nM。FK-506 is a potent immunosuppressant that forms a high affinity complex (Ki = 0.2 nM) with FK-506 binding protein 12 (FKBP12). This complex inhibits the activity of the calcium/calmodulin-dependent protein phosphatase, calcineurin, leading to disruption of T-cell activation. SLF is a cell-permeable analog of FK-506 that binds tightly to FKBP but lacks the ability to inhibit calcineurin. By itself, SLF does not exhibit a significant cellular response. However, homodimers of SLF or heterodimers with another protein ligand, provide a method to promote the dimerization of ligand-specific fusion proteins to induce signaling events within a cellular environment. For example, SLF monomers connected with a 10-atom linker activates Fas signaling via Fas-FKBP fusion proteins with an EC50 of 6 nM.