R18 TFA is a peptide antagonist of 14-3-3, with KD of 70-90nM [1]. R18 TFA can inhibit all members of the 14-3-3 protein family with a very similar affinity coefficient, and effectively utilize the amphiphilicity of the 14-3-3 binding channel to competitively inhibit phosphorylation and non-14-3-3-dependent protein-protein interactions [2]. Disruption of 14-3-3 via the R18 TFA switches nerve growth factor- and myelin-associated glycoprotein-dependent repulsion to attraction in rat DRG neurons [3]. The R18 TFA has been widely used to disrupt the binding of 14-3-3 to the ligands, thereby screening out the proteins that are regulated by 14-3-3[4].
In vitro, R18 TFA treatment at 8μM for 48 hours significantly inhibited the viability of MMQ cells and reduced the expression of 14-3-3η[5].
References:
[1] Wang B, Yang H, Liu Y C, et al. Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display[J]. Biochemistry, 1999, 38(38): 12499-12504.
[2] Liu J, Cao S, Ding G, et al. The role of 14‐3‐3 proteins in cell signalling pathways and virus infection[J]. Journal of cellular and molecular medicine, 2021, 25(9): 4173-4182.
[3] Kent C B, Shimada T, Ferraro G B, et al. 14-3-3 proteins regulate protein kinase a activity to modulate growth cone turning responses[J]. Journal of Neuroscience, 2010, 30(42): 14059-14067.
[4] Repton C, Cullen C F, Costa M F A, et al. The phospho-docking protein 14-3-3 regulates microtubule-associated proteins in oocytes including the chromosomal passenger Borealin[J]. PLoS Genetics, 2022, 18(6): e1009995.
[5] Zhao S, Li B, Li C, et al. The apoptosis regulator 14-3-3η and its potential as a therapeutic target in pituitary oncocytoma[J]. Frontiers in endocrinology, 2019, 10: 797.
R18 TFA是一种14-3-3的肽类拮抗剂，KD值为70-90nM[1]。R18 TFA能以非常相似的亲和系数抑制14-3-3蛋白家族的所有成员，并有效利用14-3-3结合通道的两亲性，竞争性地抑制磷酸化及非14-3-3依赖的蛋白质-蛋白质相互作用[2]。通过R18 TFA破坏14-3-3，可使大鼠背根神经节神经元中神经生长因子和髓鞘相关糖蛋白依赖性排斥转变为吸引[3]。R18 TFA已被广泛用于破坏14-3-3与配体的结合，从而筛选出受14-3-3调控的蛋白质[4]。
在体外，使用8µM的R18 TFA处理48小时，显著抑制了MMQ细胞的活力，并降低了14-3-3η的表达[5]。